The Cancer Genome Atlas Program (TCGA) - NCI
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Japan, Tokyo
Department of Health and Human Services National Institutes of Health National Cancer Institute USA
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相关论文
425ASF1a inhibition induces p53-dependent growth arrest and senescence of cancer cells
Yujiao Wu•Xidan Li•Jingya Yu•Magnus Björkholm•Dawei Xu
Cell Death & Disease
2019
•2019/1/28
•Vol.10 No.2 p.1-15
Anti-silencing function 1a (ASF1a) is a histone H3–H4 chaperone isoform involved in chromatin assembling and transcription regulation. Recently, ASF1a has been shown to be up-regulated in certain human malignancies and required for the expression of telomerase reverse transcriptase (TERT), a factor ...
Cancer epigeneticsCell deathLiver cancerOncogenesSenescence
10.1038/S41419-019-1357-Z
ISSN:2041-4889
The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets
Hu Zhongyi•Yuan Jiao•Long Meixiao•Jiang Junjie•Zhang Youyou等 15 人
Nature Cancer
2021
•2021/12/13
•00 p.1-17
Cell-surface proteins (SPs) are a rich source of immune and targeted therapies. By systematically integrating single-cell and bulk genomics, functional studies and target actionability, in the present study we comprehensively identify and annotate genes encoding SPs (GESPs) pan-cancer. We characteri...
CancerCancer genomicsCancer therapyTumour immunology
10.1038/S43018-021-00282-W
ISSN:2662-1347
hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer
Fengjiang Qin•Yuya Wang•Chenyue Yang•Yifei Ren•Qinglv Wei等 20 人
Nature Communications
2025
•2025/5/24
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Ovarian cancer has the highest mortality rate among gynecologic tumors worldwide, with unclear underlying mechanisms of pathogenesis. RNA-binding proteins (RBPs) primarily direct post-transcriptional regulation through modulating RNA metabolism. Recent evidence demonstrates that RBPs are also implic...
Ovarian cancerTranscription
10.1038/S41467-025-60115-7
ISSN:2041-1723
Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark
Luopin Wang•Aryamav Pattnaik•Subhransu Sekhar Sahoo•Ella G. Stone•Yuxin Zhuang等 28 人
Nature Communications
2024
•2024/8/24
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Correctly identifying perturbed biological pathways is a critical step in uncovering basic disease mechanisms and developing much-needed therapeutic strategies. However, whether current tools are optimal for unbiased discovery of relevant pathways remains unclear. Here, we create “Benchmark” to crit...
Cancer genomicsComputational biology and bioinformaticsDrug discoveryPrognostic markersTumour biomarkers
10.1038/S41467-024-51859-9
ISSN:2041-1723
USP44 regulates irradiation-induced DNA double-strand break repair and suppresses tumorigenesis in nasopharyngeal carcinoma
Chen Yang•Zhao Yin•Yang Xiaojing•Ren Xianyue•Huang Shengyan等 16 人
Nature Communications
2022
•2022/1/25
•Vol.13 No.1 p.1-16
Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC), and approximately 20% of patients experience treatment failure due to tumour radioresistance. However, the exact regulatory mechanism remains poorly understood. Here, we show that the deubiquitinase USP44 is hype...
DNA methylationHead and neck cancerRadiotherapyTumour-suppressor proteins
10.1038/S41467-022-28158-2
ISSN:2041-1723
Pan-cancer analysis reveals TAp63-regulated oncogenic lncRNAs that promote cancer progression through AKT activation
Marco Napoli•Xiaobo Li•Hayley D. Ackerman•Avani A. Deshpande•Ivan Barannikov等 17 人
Nature Communications
2020
•2020/10/14
•Vol.11 No.1 p.1-16
The most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of the PI3K/AKT pathway, two events crucial for cancer progression. Mutations in TP53 lead to the inhibition of the tumour and metastasis suppressor TAp63, a p53 family member. By performing ...
Long non-coding RNAsMetastasis
10.1038/S41467-020-18973-W
ISSN:2041-1723
Brain–heart–eye axis revealed by multi-organ imaging genetics and proteomics
Aleix Boquet-Pujadas•Filippos Anagnostakis•Michael R. Duggan•Cassandra M. Joynes•Arthur W. Toga等 9 人
Nature Biomedical Engineering
2025
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Multi-organ research investigates interconnections among multiple human organ systems, enhancing our understanding of human aging and disease mechanisms. Here we use multi-organ imaging, individual- and summary-level genetics, and proteomics data consolidated via the MULTI Consortium to delineate a ...
Genetics researchHeritable quantitative traitMachine learning
10.1038/S41551-025-01506-5
ISSN:2157-846X
HIF sustain a transcriptional regulatory circuit of EPAS1 expression in renal clear cell carcinoma
Stephanie Naas•René Krüger•Steffen Grampp•Victoria Lauer•Andre Kraus等 13 人
Nature Communications
2026
•2026/2/19
•Vol.17 No.1 p.17640
Initiation and sustainment of oncogenic signaling is a hallmark of cancer evolution and progression. In renal clear cell carcinoma, loss of von Hippel-Lindau protein causes stabilization of hypoxia-inducible transcription factors (HIF) evoking a pseudo-hypoxic response, perturbing epithelial homeost...
Gene regulationRenal cell carcinoma
10.1038/S41467-026-68576-0
ISSN:2041-1723
Mapping phospho-catalytic dependencies of therapy-resistant tumours reveals actionable vulnerabilities
Jean-Philippe Coppé•Miki Mori•Bo Pan•Christina Yau•Denise M. Wolf等 20 人
Nature Cell Biology
2019
•2019/6/3
•Vol.21 No.6 p.778-790
Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a practical high-throughput system to measure the enzymatic activity of kinases using biological peptide targ...
Biochemical networksCancerCancer therapeutic resistanceProteomic analysis
10.1038/S41556-019-0328-Z
ISSN:1465-7392
PLCγ1 suppression promotes the adaptation of KRAS-mutant lung adenocarcinomas to hypoxia
Maria Saliakoura•Matteo Rossi Sebastiano•Chiara Pozzato•Florian H. Heidel•Tina M. Schnöder等 14 人
Nature Cell Biology
2020
•2020/10/19
•Vol.22 No.11 p.1382-1395
Mutant KRAS modulates the metabolic plasticity of cancer cells to confer a growth advantage during hypoxia, but the molecular underpinnings are largely unknown. Using a lipidomic screen, we found that PLCγ1 is suppressed during hypoxia in KRAS-mutant human lung adenocarcinoma cancer cell lines. Supp...
Cancer metabolismLung cancerNon-small-cell lung cancerPhospholipids
10.1038/S41556-020-00592-8
ISSN:1465-7392
Development and validation of a deep learning algorithm for improving Gleason scoring of prostate cancer
Kunal Nagpal•Davis Foote•Yun Liu•Po-Hsuan Cameron Chen•Ellery Wulczyn等 19 人
Npj Digital Medicine
2019
•2019/6/7
•Vol.2 No.1 p.1-10
For prostate cancer patients, the Gleason score is one of the most important prognostic factors, potentially determining treatment independent of the stage. However, Gleason scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility. Here we pres...
Prostate cancer
10.1038/S41746-019-0112-2
ISSN:2398-6352
A micropeptide encoded by the lncRNA USP30-AS1 promotes tumor growth by attenuating cGAS–STING–type I IFN signaling in macrophages
Xingwen Wang•Yi Zhang•Jiangwen Ma•Qingyu Lin•Zhenghang Wang等 18 人
Nature Cancer
2026
•2026/7/9
•00 p.1-17
Immune checkpoint blockade has achieved remarkable success in cancer treatment; however, enhancing its efficacy remains a challenge. Here we identified an immunoregulatory micropeptide encoded by the long noncoding RNA USP30-AS1 gene, highly expressed in tumor-associated macrophages. The so-designat...
CancerCancer microenvironmentTumour immunology
10.1038/S43018-026-01195-2
ISSN:2662-1347
Synthetic lethality of mRNA quality control complexes in cancer
Vivian Prindle•Adam E. Richardson•Kimberly R. Sher•Sarah Kongpachith•Kaitlin Kentala等 25 人
Nature
2025
•2025/2/5
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Synthetic lethality exploits the genetic vulnerabilities of cancer cells to enable a targeted, precision approach to treat cancer1. Over the past 15 years, synthetic lethal cancer target discovery approaches have led to clinical successes of PARP inhibitors2 and ushered several next-generation thera...
CancerTarget identificationTarget validationTumour biomarkersTumour-suppressor proteins
10.1038/S41586-024-08398-6
ISSN:0028-0836
N6-methyladenosine (m6A) in 18S rRNA promotes fatty acid metabolism and oncogenic transformation
Peng Hao•Chen Binbin•Wei Wei•Guo Siyao•Han Hui等 11 人
Nature Metabolism
2022
•2022/8/23
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Aberrant RNA modifications lead to dysregulated gene expression and cancer progression. Ribosomal RNA (rRNA) accounts for more than 80% of a cell’s total RNA, but the functions and molecular mechanisms underlying rRNA modifications in cancers are poorly understood. Here, we show that the 18S rRNA N6...
BiochemistryBiological techniquesCancerLipidsMetabolism
10.1038/S42255-022-00622-9
ISSN:2522-5812
PAPOLA-mediated hyperactive polyadenylation promotes leukemogenesis and leukemia stem cell self-renewal through metabolic reprogramming
Siyao Guo•Yutong Zou•Canfeng Zhang•Hui Han•Yishan Li等 19 人
Nature Cancer
2026
•2026/7/15
•00 p.1-19
Polyadenylation is essential for mRNA stability and translational efficiency. Although poly(A) tail length is dynamically regulated under physiological conditions, its dysregulation and functional importance in cancer remain poorly understood. Here, we identify widespread poly(A) tail elongation and...
CancerLeukaemia
10.1038/S43018-026-01190-7
ISSN:2662-1347
Therapeutic targeting of the mevalonate–geranylgeranyl diphosphate pathway with statins overcomes chemotherapy resistance in small cell lung cancer
Guo Chenchen•Wan Ruijie•He Yayi•Lin Shu-Hai•Cao Jiayu等 19 人
Nature Cancer
2022
•2022/4/21
•00 p.1-15
Small cell lung cancer (SCLC) lacks effective treatments to overcome chemoresistance. Here we established multiple human chemoresistant xenograft models through long-term intermittent chemotherapy, mimicking clinically relevant therapeutic settings. We show that chemoresistant SCLC undergoes metabol...
CancerCancer metabolismCancer therapeutic resistance
10.1038/S43018-022-00358-1
ISSN:2662-1347
Targeting cysteinyl leukotriene receptor 1 reprograms tumor-promoting myelopoiesis and overcomes immune checkpoint therapy resistance
Hui Tang•Ping Xie•Jihae Ahn•Mi-Ran Choi•Jie Fan等 8 人
Nature Cancer
2026
•2026/5/19
•00 p.1-19
‘Emergency’ myelopoiesis usually occurs to facilitate malignancy progression. Immunosuppressive neutrophils, also termed polymorphonuclear myeloid-derived suppressor cells, are potent mediators of immunosuppression and tumor promotion. Here we demonstrate that the STAT3-dependent induction of cystei...
Adaptive immunityCancerTumour immunology
10.1038/S43018-026-01174-7
ISSN:2662-1347
A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry
Andrea Cortese•Sarah J. Beecroft•Stefano Facchini•Riccardo Curro•Macarena Cabrera-Serrano等 54 人
Nature Communications
2024
•2024/7/27
•Vol.15 No.1 p.1-15
Oculopharyngodistal myopathy (OPDM) is an inherited myopathy manifesting with ptosis, dysphagia and distal weakness. Pathologically it is characterised by rimmed vacuoles and intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified ...
Medical geneticsNeuromuscular disease
10.1038/S41467-024-49950-2
ISSN:2041-1723
Persistent mutation burden drives sustained anti-tumor immune responses
Niknafs Noushin•Balan Archana•Cherry Christopher•Hummelink Karlijn•Monkhorst Kim等 21 人
Nature Medicine
2023
•2023/1/26
•Vol.29 No.2 p.440-449
Tumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses in the context of immunotherapy. We evaluated mutations in regions of the genome that are unlikely to undergo loss in a pan-cancer analysis a...
Cancer genomicsImmunotherapyMedical genomics
10.1038/S41591-022-02163-W
ISSN:1078-8956
RNA sequestration in P-bodies sustains myeloid leukaemia
Srikanth Kodali•Ludovica Proietti•Gemma Valcarcel•Anna V. López-Rubio•Patrizia Pessina等 32 人
Nature Cell Biology
2024
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•00 p.1-14
Post-transcriptional mechanisms are fundamental safeguards of progenitor cell identity and are often dysregulated in cancer. Here, we identified regulators of P-bodies as crucial vulnerabilities in acute myeloid leukaemia (AML) through genome-wide CRISPR screens in normal and malignant haematopoieti...
CancerRNATumour-suppressor proteins
10.1038/S41556-024-01489-6
ISSN:1465-7392
An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1
Aftab Fareesa•Rodriguez-Fuguet Alice•Silva Luis•Kobayashi Ikei S.•Sun Jiao等 10 人
British Journal Of Cancer
2023
•2023/2/21
•00 p.1-18
Lung cancer cells overexpress mucin 1 (MUC1) and active subunit MUC1-CT. Although a peptide blocks MUC1 signalling, metabolites targeting MUC1 are not well studied. AICAR is a purine biosynthesis intermediate. Cell viability and apoptosis were measured in AICAR-treated EGFR-mutant and wild-type lung...
Non-small-cell lung cancerTargeted therapies
10.1038/S41416-023-02196-Z
ISSN:0007-0920
Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides
Humberto J. Ferreira•Brian J. Stevenson•HuiSong Pak•Fengchao Yu•Jessica Almeida Oliveira等 15 人
Nature Communications
2024
•2024/3/15
•Vol.15 No.1 p.1-18
Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5’ cap and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed circRNAs in human cancers could be an unexplored source of tumor-specifi...
Antigen processing and presentationTumour immunology
10.1038/S41467-024-46408-3
ISSN:2041-1723
Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer
Zhe Jiang•YoungJun Ju•Amjad Ali•Philip E. D. Chung•Patryk Skowron等 21 人
Nature Communications
2023
•2023/7/18
•Vol.14 No.1 p.1-22
Metastatic breast-cancer is a major cause of death in women worldwide, yet the relationship between oncogenic drivers that promote metastatic versus primary cancer is still contentious. To elucidate this relationship in treatment-naive animals, we hereby describe mammary-specific transposon-mutagene...
Breast cancerCancer genomicsCancer modelsMetastasisMutagenesis
10.1038/S41467-023-39935-Y
ISSN:2041-1723
Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias
Ricardo de Matos Simoes•Ryosuke Shirasaki•Sondra L. Downey-Kopyscinski•Geoffrey M. Matthews•Benjamin G. Barwick等 41 人
Nature Cancer
2023
•2023/5/26
•Vol.4 No.5 p.754-773
Clinical progress in multiple myeloma (MM), an incurable plasma cell (PC) neoplasia, has been driven by therapies that have limited applications beyond MM/PC neoplasias and do not target specific oncogenic mutations in MM. Instead, these agents target pathways critical for PC biology yet largely dis...
CancerCancer genomicsMyeloma
10.1038/S43018-023-00550-X
ISSN:2662-1347
Integrating bulk, single-cell, and spatial transcriptomics to identify and functionally validate novel targets to enhance immunotherapy in NSCLC
Kui Cao•Shenshui Wei•Tianjiao Ma•Xinxin Yang•Yuning Wang等 14 人
Npj Precision Oncology
2025
•2025/4/16
•Vol.9 No.1 p.1-22
Programmed cell deaths (PCDs) are crucial for tumor progression. By analyzing 18 PCDs, we generated a robust multigene signature, Combined Cell Death Index (CCDI), comprising necroptosis and autophagy genes for non-small cell lung cancer (NSCLC). The CCDI accurately stratified patients by survival p...
CancerComputational biology and bioinformaticsImmunology
10.1038/S41698-025-00893-X
ISSN:2397-768X
piRNA-independent function of PIWIL1 as a co-activator for anaphase promoting complex/cyclosome to drive pancreatic cancer metastasis
Feng Li•Peng Yuan•Ming Rao•Chun-Hui Jin•Wei Tang等 18 人
Nature Cell Biology
2020
•2020/3/16
•Vol.22 No.4 p.425-438
Piwi proteins are normally restricted in germ cells to suppress transposons through associations with Piwi-interacting RNAs (piRNAs), but they are also frequently activated in many types of human cancers. A great puzzle is the lack of significant induction of corresponding piRNAs in cancer cells, as...
CancerCell biologyDiseasesMicrobiology
10.1038/S41556-020-0486-Z
ISSN:1465-7392
Epigenetic silencing of the ubiquitin ligase subunit FBXL7 impairs c-SRC degradation and promotes epithelial-to-mesenchymal transition and metastasis
Loredana Moro•Daniele Simoneschi•Emma Kurz•Arnaldo A. Arbini•Shaowen Jang等 18 人
Nature Cell Biology
2020
•2020/8/24
•Vol.22 No.9 p.1130-1142
Epigenetic plasticity is a pivotal factor that drives metastasis. Here, we show that the promoter of the gene that encodes the ubiquitin ligase subunit FBXL7 is hypermethylated in advanced prostate and pancreatic cancers, correlating with decreased FBXL7 mRNA and protein levels. Low FBXL7 mRNA level...
Cancer epigeneticsMetastasisTargeted therapiesUbiquitin ligases
10.1038/S41556-020-0560-6
ISSN:1465-7392
Development and validation of an autonomous artificial intelligence agent for clinical decision-making in oncology
Dyke Ferber•Omar S. M. El Nahhas•Georg Wölflein•Isabella C. Wiest•Jan Clusmann等 14 人
Nature Cancer
2025
•2025/6/6
•00 p.1-13
Clinical decision-making in oncology is complex, requiring the integration of multimodal data and multidomain expertise. We developed and evaluated an autonomous clinical artificial intelligence (AI) agent leveraging GPT-4 with multimodal precision oncology tools to support personalized clinical dec...
CancerCancer therapyData integrationInformation technology
10.1038/S43018-025-00991-6
ISSN:2662-1347
Evolving cell states and oncogenic drivers during the progression of IDH-mutant gliomas
Jingyi Wu•L. Nicolas Gonzalez Castro•Sofia Battaglia•Chadi A. El Farran•Joshua P. D’Antonio等 8 人
Nature Cancer
2024
•2024/11/21
•00 p.1-13
Isocitrate dehydrogenase (IDH) mutants define a class of gliomas that are initially slow-growing but inevitably progress to fatal disease. To characterize their malignant cell hierarchy, we profiled chromatin accessibility and gene expression across single cells from low-grade and high-grade IDH-mut...
CancerCancer genomicsChromatin
10.1038/S43018-024-00865-3
ISSN:2662-1347
KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway
Yitong Xu•Chenglong Wang•Xizi Jiang•Yao Zhang•Hongbo Su等 8 人
Cell Death & Disease
2021
•2021/5/28
•Vol.12 No.6 p.1-14
Lung cancer is the leading cause of cancer-related death worldwide. KLHL38 has been reported to be upregulated during diapause but downregulated after androgen treatment during the reversal of androgen-dependent skeletal muscle atrophy. This study aimed to clarify the role of KLHL38 in non-small cel...
Lung cancerOncogenesis
10.1038/S41419-021-03835-0
ISSN:2041-4889
Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions
Keyang Xu•Ai Fu•Zhaoyi Li•Liangbin Miao•Zhonghan Lou等 12 人
Nature Communications
2024
•2024/2/24
•Vol.15 No.1 p.1-17
The cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that in obesity, extracellular matrix protein 1 (ECM1) protein levels are significantly increased in circulating sEVs, which is dependent on integrin-β2. Knockdown of integrin-β2 does not a...
Breast cancerMechanisms of disease
10.1038/S41467-024-45995-5
ISSN:2041-1723
N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis
Han Hui•Yang Chunlong•Ma Jieyi•Zhang Shuishen•Zheng Siyi等 19 人
Nature Communications
2022
•2022/3/18
•Vol.13 No.1 p.1-15
Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m7G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squa...
CancerPost-translational modifications
10.1038/S41467-022-29125-7
ISSN:2041-1723
O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1
Zhu Qiang•Zhou Hong•Wu Liming•Lai Zhenyuan•Geng Didi等 12 人
Nature Chemical Biology
2022
•2022/7/25
•00 p.1-9
Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. However, little is known about how this pathway is regulated. Here we demonstrate that Kras mutation induces cellular O-linked β-N-acetylglucosa...
CancerComputational chemistryGlycobiologyMetabolismPost-translational modifications
10.1038/S41589-022-01085-5
ISSN:1552-4450
MRI transformer deep learning and radiomics for predicting IDH wild type TERT promoter mutant gliomas
Wenju Niu•Junyu Yan•Min Hao•Yibo Zhang•Tianshi Li等 15 人
Npj Precision Oncology
2025
•2025/3/27
•Vol.9 No.1 p.1-12
This study aims to predict IDH wt with TERTp-mut gliomas using multiparametric MRI sequences through a novel fusion model, while matching model classification metrics with patient risk stratification aids in crafting personalized diagnostic and prognosis evaluations.Preoperative T1CE and T2FLAIR seq...
BiomarkersCNS cancerDiagnostic markersOncology
10.1038/S41698-025-00884-Y
ISSN:2397-768X
Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1/CXCR2 results in antitumor immunity and durable response in pancreatic cancer
Gulhati Pat•Schalck Aislyn•Jiang Shan•Shang Xiaoying•Wu Chang-Jiun等 26 人
Nature Cancer
2022
•2022/12/30
•Vol.4 No.1 p.62-80
Pancreatic ductal adenocarcinoma (PDAC) is considered non-immunogenic, with trials showing its recalcitrance to PD1 and CTLA4 immune checkpoint therapies (ICTs). Here, we sought to systematically characterize the mechanisms underlying de novo ICT resistance and to identify effective therapeutic opti...
CancerCancer immunotherapyImmunologyPancreatic cancer
10.1038/S43018-022-00500-Z
ISSN:2662-1347
Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy
Luca Licata•Marco Barreca•Barbara Galbardi•Matteo Dugo•Giulia Viale等 11 人
British Journal Of Cancer
2023
•2023/11/7
•00 p.1-9
Luminal breast cancers with high proliferation (MKShi) and low ER-related signalling (ERSlo) have a poor prognosis. We investigated treatment responses and molecular features of MKShi/ERSlo tumours to inform potential therapies. Gene expression data from patients who received neoadjuvant chemotherap...
BiomarkersTranslational research
10.1038/S41416-023-02477-7
ISSN:0007-0920
Polymer-locking fusogenic liposomes for glioblastoma-targeted siRNA delivery and CRISPR–Cas gene editing
Yu Zhao•Jie Qin•Daohan Yu•Yuxiang Liu•Dan Song等 22 人
Nature Nanotechnology
2024
•2024/8/29
•00 p.1-11
In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR–Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is c...
Drug deliveryNanoparticlesNanotechnology in cancer
10.1038/S41565-024-01769-0
ISSN:1748-3387
CDK10 suppresses nucleic acid sensors-mediated antitumor immunity
Gaoshan Xu•Fusheng Guo•Chuan He•Xiyong Wang•Bolin Xiang等 22 人
Nature Cancer
2026
•2026/1/8
•Vol.7 No.2 p.283-303
Cancer immunotherapies have revolutionized cancer treatment, yet many patients fail to respond. Activating innate immunity offers a promising approach to enhance therapeutic efficacy, but the signaling kinases directly regulating this process to boost antitumor responses remain elusive. Here we cond...
CancerCell signallingTumour immunology
10.1038/S43018-025-01100-3
ISSN:2662-1347
Engineered BCG selectively triggers trained immunity in tumor-associated macrophages and sensitizes glioblastoma to radiotherapy in mice
Ke Ren•Ziyang Yuan•Lei Lei•Ziyuan Xiao•Ningyi Ma等 14 人
Nature Communications
2026
•2026/4/20
0Radiotherapy plays a crucial role in antitumor immunity in glioblastoma, yet its efficacy is often limited, resulting in tumor recurrence. Here, we engineer a macrophage membrane-camouflaged Bacillus Calmette-Guérin (BCG) via bioorthogonal chemistry to enhance radiotherapy against glioblastoma. This...
BiotechnologyRadiotherapyTumour immunology
10.1038/S41467-026-72067-7
ISSN:2041-1723
Blocking methionine catabolism induces senescence and confers vulnerability to GSK3 inhibition in liver cancer
Fuming Li•Pingyu Liu•Wen Mi•Liucheng Li•Nicole M. Anderson等 14 人
Nature Cancer
2024
•2024/1/2
•00 p.1-16
Availability of the essential amino acid methionine affects cellular metabolism and growth, and dietary methionine restriction has been implicated as a cancer therapeutic strategy. Nevertheless, how liver cancer cells respond to methionine deprivation and underlying mechanisms remain unclear. Here w...
CancerCancer therapy
10.1038/S43018-023-00671-3
ISSN:2662-1347
IdentifiHR predicts homologous recombination deficiency in high-grade serous ovarian carcinoma using gene expression
Ashley L. Weir•Samuel C. Lee•Mengbo Li•Ahwan Pandey•Chin Wee Tan等 8 人
Communications Medicine
2026
•2026/1/14
•Vol.6 No.1 p.1190
Approximately half of all high-grade serous ovarian carcinomas (HGSCs) have a therapeutically targetable defect in homologous recombination (HR) DNA repair. While there are genomic and transcriptomic methods, developed for other cancers, to identify HR deficient (HRD) samples, there are no gene expr...
Cancer genomicsComputational biology and bioinformaticsOvarian cancer
10.1038/S43856-026-01387-Y
ISSN:2730-664X
Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma
Daniel Schäfer•Stefan Tomiuk•Laura N. Küster•Wa’el Al Rawashdeh•Janina Henze等 22 人
Nature Communications
2021
•2021/3/5
•Vol.12 No.1 p.1-18
A major roadblock prohibiting effective cellular immunotherapy of pancreatic ductal adenocarcinoma (PDAC) is the lack of suitable tumor-specific antigens. To address this challenge, here we combine flow cytometry screenings, bioinformatic expression analyses and a cyclic immunofluorescence platform....
Gastrointestinal cancerImmunotherapyPreclinical researchTarget identificationTarget validation
10.1038/S41467-021-21774-4
ISSN:2041-1723
Global loss of promoter–enhancer connectivity and rebalancing of gene expression during early colorectal cancer carcinogenesis
Yizhou Zhu•Hayan Lee•Shannon White•Annika K. Weimer•Emma Monte等 26 人
Nature Cancer
2024
•2024/10/30
•00 p.1-16
Although three-dimensional (3D) genome architecture is crucial for gene regulation, its role in disease remains elusive. We traced the evolution and malignant transformation of colorectal cancer (CRC) by generating high-resolution chromatin conformation maps of 33 colon samples spanning different st...
CancerCancer genomicsChromatin structureDynamic networksGenome-wide analysis of gene expression
10.1038/S43018-024-00823-Z
ISSN:2662-1347
Phospholipase Cγ1 (PLCG1) overexpression is associated with tumor growth and poor survival in IDH wild-type lower-grade gliomas in adult patients
Li Tianwen•Yang Zhipeng•Li Haoyuan•Zhu Jingjing•Wang Ye等 7 人
Laboratory Investigation
2021
•2021/10/25
•00 p.1-11
Gliomas are the most common and recalcitrant intracranial tumors, approximately a quarter of which are classified as lower-grade gliomas (WHO II–III). Although the prognosis of lower-grade gliomas (LGGs) is significantly better than that of higher-grade gliomas, as a highly heterogeneous tumor type,...
Cancer epigeneticsCNS cancerGenetic markers
10.1038/S41374-021-00682-7
ISSN:0023-6837
Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation
Ping-Hsiu Wu•Yasuhito Onodera•Amato J. Giaccia•Quynh-Thu Le•Shinichi Shimizu等 7 人
Communications Biology
2020
•2020/10/27
•Vol.3 No.1 p.1-15
Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by ...
Breast cancerCancer microenvironmentLysosomes
10.1038/S42003-020-01339-9
ISSN:2399-3642
ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer
Napoli Marco•Wu Sarah J.•Gore Bethanie L.•Abbas Hussein•Lee Kyubum等 12 人
Nature Communications
2022
•2022/2/1
•Vol.13 No.1 p.1-16
Distinct lung stem cells give rise to lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). ΔNp63, the p53 family member and p63 isoform, guides the maturation of these stem cells through the regulation of their self-renewal and terminal differentiation; however, the underlying mechanistic ...
Cancer stem cellsNon-small-cell lung cancer
10.1038/S41467-022-28202-1
ISSN:2041-1723
Comprehensive prediction and analysis of human protein essentiality based on a pretrained large language model
Boming Kang•Rui Fan•Chunmei Cui•Qinghua Cui
Nature Computational Science
2024
•2024/11/27
•00 p.1-11
Human essential proteins (HEPs) are indispensable for individual viability and development. However, experimental methods to identify HEPs are often costly, time consuming and labor intensive. In addition, existing computational methods predict HEPs only at the cell line level, but HEPs vary across ...
Computational modelsMachine learning
10.1038/S43588-024-00733-1
ISSN:2662-8457
CAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes
Sameeha Jilani•Justin D. Saco•Edurne Mugarza•Aleida Pujol-Morcillo•Jeffrey Chokry等 20 人
Nature Communications
2024
•2024/2/9
•Vol.15 No.1 p.1-19
A major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T cell therapy target to treat patients with cutane...
Cancer immunotherapyImmunotherapyMelanoma
10.1038/S41467-024-45221-2
ISSN:2041-1723
Immune evasion mechanisms in early-stage I high-grade serous ovarian carcinoma: insights into regulatory T cell dynamics
Joanna Mikulak•Sara Terzoli•Paolo Marzano•Valentina Cazzetta•Giampaolo Martiniello等 18 人
Cell Death & Disease
2025
•2025/4/1
•Vol.16 No.1 p.1-16
The mechanisms driving immune evasion in early-stage I high-grade serous ovarian carcinoma (HGSOC) remain poorly understood. To investigate this, we performed single-cell RNA-sequencing analysis. Our findings revealed a highly immunosuppressive HGSOC microenvironment, characterized by abundant infil...
Immune evasionImmunosurveillanceOvarian cancer
10.1038/S41419-025-07557-5
ISSN:2041-4889
FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity
Xinnan Liu•Weiqi Zhang•Yichao Han•Hao Cheng•Qi Liu等 21 人
Nature Communications
2024
•2024/1/2
•Vol.15 No.1 p.1-16
Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors....
Cancer microenvironmentImmunosuppressionRegulatory T cellsTumour immunology
10.1038/S41467-023-44391-9
ISSN:2041-1723
MOG analogues to explore the MCT2 pharmacophore, α-ketoglutarate biology and cellular effects of N-oxalylglycine
Fets Louise•Bevan Natalie•Nunes Patrícia M.•Campos Sebastien•dos Santos Mariana Silva等 9 人
Communications Biology
2022
•2022/8/26
•Vol.5 No.1 p.1-11
α-ketoglutarate (αKG) is a central metabolic node with a broad influence on cellular physiology. The αKG analogue N-oxalylglycine (NOG) and its membrane-permeable pro-drug derivative dimethyl-oxalylglycine (DMOG) have been extensively used as tools to study prolyl hydroxylases (PHDs) and other αKG-d...
MetabolomicsSmall molecules
10.1038/S42003-022-03805-Y
ISSN:2399-3642
DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation
Batra Rajbir Nath•Lifshitz Aviezer•Vidakovic Ana Tufegdzic•Chin Suet-Feung•Sati-Batra Ankita等 21 人
Nature Communications
2021
•2021/9/13
•Vol.12 No.1 p.1-13
DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, reduced representation bisulfite sequencing (RRBS) profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort ar...
Breast cancerEpigenomics
10.1038/S41467-021-25661-W
ISSN:2041-1723
Optimizing drug combination and mechanism analysis based on risk pathway crosstalk in pan cancer
Congxue Hu•Wanqi Mi•Feng Li•Lun Zhu•Qi Ou等 10 人
Scientific Data
2024
•2024/1/16
•Vol.11 No.1 p.1-13
Combination therapy can greatly improve the efficacy of cancer treatment, so identifying the most effective drug combination and interaction can accelerate the development of combination therapy. Here we developed a computational network biological approach to identify the effective drug which inhib...
CancerComputational biology and bioinformatics
10.1038/S41597-024-02915-Y
ISSN:2052-4463
Cell-free plasma microRNAs that identify patients with glioblastoma
Bustos Matias A.•Rahimzadeh Negin•Ryu Suyeon•Gross Rebecca•Tran Linh T.等 15 人
Laboratory Investigation
2022
•2022/1/10
•00 p.1-11
Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) a...
BiomarkersCNS cancermiRNAs
10.1038/S41374-021-00720-4
ISSN:0023-6837
Integrative multi-omics networks identify PKCδ and DNA-PK as master kinases of glioblastoma subtypes and guide targeted cancer therapy
Migliozzi Simona•Oh Young Taek•Hasanain Mohammad•Garofano Luciano•D’Angelo Fulvio等 15 人
Nature Cancer
2023
•2023/2/2
•Vol.4 No.2 p.181-202
Despite producing a panoply of potential cancer-specific targets, the proteogenomic characterization of human tumors has yet to demonstrate value for precision cancer medicine. Integrative multi-omics using a machine-learning network identified master kinases responsible for effecting phenotypic hal...
CancerCancer genomicsCNS cancerMachine learning
10.1038/S43018-022-00510-X
ISSN:2662-1347
Deep learning and transfer learning identify breast cancer survival subtypes from single-cell imaging data
Shashank Yadav•Shu Zhou•Bing He•Yuheng Du•Lana X. Garmire
Communications Medicine
2023
•2023/12/19
•Vol.3 No.1 p.1-12
Single-cell multiplex imaging data have provided new insights into disease subtypes and prognoses recently. However, quantitative models that explicitly capture single-cell resolution cell-cell interaction features to predict patient survival at a population scale are currently missing. We quantifie...
Computational biology and bioinformaticsSystems biology
10.1038/S43856-023-00414-6
ISSN:2730-664X
Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer
Malagoli Tagliazucchi Guidantonio•Wiecek Anna J.•Withnell Eloise•Secrier Maria
Nature Communications
2023
•2023/2/11
•Vol.14 No.1 p.1-20
The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based o...
Cancer genomicsData integrationEpithelial–mesenchymal transitionTumour heterogeneity
10.1038/S41467-023-36439-7
ISSN:2041-1723
Tissue-specific and interferon-inducible expression of nonfunctional ACE2 through endogenous retroelement co-option
Kevin W. Ng•Jan Attig•William Bolland•George R. Young•Jack Major等 9 人
Nature Genetics
2020
•2020/10/19
•Vol.52 No.12 p.1294-1302
Angiotensin-converting enzyme 2 (ACE2) is an entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a regulator of several physiological processes. ACE2 has recently been proposed to be interferon (IFN) inducible, suggesting that SARS-CoV-2 may exploit this phenomenon to...
Gene expressionGene regulationSARS-CoV-2
10.1038/S41588-020-00732-8
ISSN:1061-4036
In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer
Dzana Dervovic•Ahmad A. Malik•Edward L. Y. Chen•Masahiro Narimatsu•Nina Adler等 25 人
Nature Communications
2023
•2023/5/31
•Vol.14 No.1 p.1-21
How the genetic landscape governs a tumor’s response to immunotherapy remains poorly understood. To assess the immune-modulatory capabilities of 573 genes associated with altered cytotoxicity in human cancers, here we perform CRISPR/Cas9 screens directly in mouse lung cancer models. We recover the k...
ImmunotherapyNon-small-cell lung cancerOncogenesTumour immunology
10.1038/S41467-023-38841-7
ISSN:2041-1723
A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor
Carla Eller•Laura Heydmann•Che C. Colpitts•Houssein El Saghire•Federica Piccioni等 23 人
Nature Communications
2020
•2020/6/1
•Vol.11 No.1 p.1-17
Chronic HBV infection is a major cause of liver disease and cancer worldwide. Approaches for cure are lacking, and the knowledge of virus-host interactions is still limited. Here, we perform a genome-wide gain-of-function screen using a poorly permissive hepatoma cell line to uncover host factors en...
Functional genomicsHepatitis B virusViral hepatitis
10.1038/S41467-020-16517-W
ISSN:2041-1723
Patient-specific gene co-expression networks reveal novel subtypes and predictive biomarkers in lung adenocarcinoma
Patricio López-Sánchez•Federico Ávila-Moreno•Enrique Hernández-Lemus•Marieke L. Kuijjer•Jesús Espinal-Enríquez
Npj Systems Biology And Applications
2025
•2025/5/9
•Vol.11 No.1 p.1-14
Lung adenocarcinoma (LUAD) is a highly heterogenous and aggressive form of non-small cell lung cancer (NSCLC). The use of genome-wide gene co-expression networks (GCNs) has been paramount to describe changes in the transcriptional regulatory programs found between diseased and healthy states of LUAD...
CancerComputational biology and bioinformaticsRegulatory networks
10.1038/S41540-025-00522-0
ISSN:2056-7189
Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer
Y. A. Jakubek•K. Chang•S. Sivakumar•Y. Yu•M. R. Giordano等 10 人
Nature Biotechnology
2019
•2019/11/4
•Vol.38 No.1 p.90-96
Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number...
Cancer genomicsHaplotypes
10.1038/S41587-019-0297-6
ISSN:1087-0156
Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth
Lei Guo•Tingting Hong•Yi-Tsang Lee•Xue Hu•Guokai Pan等 20 人
Nature Cell Biology
2024
•2024/9/9
•00 p.1-14
The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue...
Cancer epigeneticsDNA methylation
10.1038/S41556-024-01496-7
ISSN:1465-7392
Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis
Quah Hong Sheng•Cao Elaine Yiqun•Suteja Lisda•Li Constance H.•Leong Hui Sun等 19 人
Nature Communications
2023
•2023/3/27
•Vol.14 No.1 p.1-19
Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation of pre-metastatic cells, driven by ...
Cancer microenvironmentImmune evasionMetastasisOral cancerTumour immunology
10.1038/S41467-023-37379-Y
ISSN:2041-1723
Oncogenic AURKA-enhanced N 6 -methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells
Fei Peng•Jie Xu•Bai Cui•Qilan Liang•Sai Zeng等 27 人
Cell Research
2020
•2020/8/28
•Vol.31 No.3 p.345-361
RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms. Here, we demonstrate that DROSHA interacts with β-Catenin to transactivate STC1 in an RNA cleavage-independent manner, contributing to breast cancer stem-like cell (BCSC) properti...
Breast cancerCancer stem cellsMechanisms of disease
10.1038/S41422-020-00397-2
ISSN:1001-0602
Metabolism archetype cancer cells induce protumor TREM2+ macrophages via oxLDL-mediated metabolic interplay in hepatocellular carcinoma
Tianhao Chu•Guiqi Zhu•Zheng Tang•Weifeng Qu•Rui Yang等 22 人
Nature Communications
2025
•2025/7/23
•Vol.16 No.1 p.1-25
The functional programs adopted by cancer cells and their impact on the tumor microenvironment are complex and remain unclear. Here, we identify three distinct single-cell archetypes (i.e. metabolism, stemness and inflammation) in hepatocellular carcinoma (HCC) cells, each exhibiting unique spatial ...
Cancer microenvironmentCytotoxic T cellsHepatocellular carcinomaMonocytes and macrophagesTumour immunology
10.1038/S41467-025-62132-Y
ISSN:2041-1723
Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway
Yifan Wang•Ruocen Liao•Xingyu Chen•Xuhua Ying•Guanping Chen等 7 人
Cell Death & Disease
2020
•2020/7/9
•Vol.11 No.7 p.1-12
Breast cancer is considered to be the most prevalent cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of cancer cells. However, the functions and underlying mechanis...
Breast cancerEpithelial–mesenchymal transition
10.1038/S41419-020-2725-4
ISSN:2041-4889
Towards interpretable prediction of recurrence risk in breast cancer using pathology foundation models
Jakub R. Kaczmarzyk•Sarah C. Van Alsten•Alyssa J. Cozzo•Rajarsi Gupta•Peter K. Koo等 8 人
Npj Digital Medicine
2026
•2026/1/16
•Vol.9 No.1 p.1490
Transcriptomic assays such as the PAM50-based ROR-P score guide recurrence risk stratification in non-metastatic, ER-positive, HER2-negative breast cancer but are not universally accessible. Histopathology is routinely available and may offer a scalable alternative. We introduce MAKO, a benchmarking...
Computational biology and bioinformaticsComputational modelsMachine learningMedical imagingPrognostic markersSoftware
10.1038/S41746-025-02334-2
ISSN:2398-6352
An assessment of prognostic immunity markers in breast cancer
Benlong Yang•Jeff Chou•Yaozhong Tao•Dengbin Wu•Xinhong Wu等 16 人
Npj Breast Cancer
2018
•2018/10/29
•Vol.4 No.1 p.1-9
Tumor-infiltrating lymphocytes (TIL) and immunity gene signatures have been reported to be significantly prognostic in breast cancer but have not yet been applied for calculation of risk of recurrence in clinical assays. A compact set of 17 immunity genes was derived herein from an Affymetrix-derive...
Breast cancerPrognostic markers
10.1038/S41523-018-0088-0
ISSN:2374-4677
Transcript-targeted antigen mapping reveals the potential of POSTN splicing junction epitopes in glioblastoma immunotherapy
Zujian Xiong•Chaim T. Sneiderman•Chloe R. Kuminkoski•Jared Reinheimer•Lance Schwegman等 16 人
Genes & Immunity
2025
•2025/4/3
•00 p.1-10
Tumor antigens are crucial for T-cell mediated immunotherapy, but identified antigens for gliomas remain limited. Aberrant splicing variants are commonly expressed in tumors, resulting in unique tumor isoforms with potential antigenic properties. Herein, we analyzed multi-omics data from 587 glioma ...
Cancer geneticsImmunotherapyNext-generation sequencingTranscriptomics
10.1038/S41435-025-00326-6
ISSN:1476-5470
Strength of immune selection in tumors varies with sex and age
Andrea Castro•Rachel Marty Pyke•Xinlian Zhang•Wesley Kurt Thompson•Chi-Ping Day等 8 人
Nature Communications
2020
•2020/8/17
•Vol.11 No.1 p.1-9
Individual MHC genotype constrains the mutational landscape during tumorigenesis. Immune checkpoint inhibition reactivates immunity against tumors that escaped immune surveillance in approximately 30% of cases. Recent studies demonstrated poorer response rates in female and younger patients. Althoug...
Cancer genomicsTumour immunology
10.1038/S41467-020-17981-0
ISSN:2041-1723
Biophysical properties of AKAP95 protein condensates regulate splicing and tumorigenesis
Wei Li•Jing Hu•Bi Shi•Francesco Palomba•Michelle A. Digman等 7 人
Nature Cell Biology
2020
•2020/7/27
•Vol.22 No.8 p.960-972
It remains unknown if biophysical or material properties of biomolecular condensates regulate cancer. Here we show that AKAP95, a nuclear protein that regulates transcription and RNA splicing, plays an important role in tumorigenesis by supporting cancer cell growth and suppressing oncogene-induced ...
CancerGene expressionRNA splicing
10.1038/S41556-020-0550-8
ISSN:1465-7392
The Glycolytic Gatekeeper PDK1 defines different metabolic states between genetically distinct subtypes of human acute myeloid leukemia
Erdem Ayşegül•Marin Silvia•Pereira-Martins Diego A.•Cortés Roldán•Cunningham Alan等 15 人
Nature Communications
2022
•2022/3/1
•Vol.13 No.1 p.1-16
Acute myeloid leukemia remains difficult to treat due to strong genetic heterogeneity between and within individual patients. Here, we show that Pyruvate dehydrogenase kinase 1 (PDK1) acts as a targetable determinant of different metabolic states in acute myeloid leukemia (AML). PDK1low AMLs are OXP...
Acute myeloid leukaemiaCancer metabolism
10.1038/S41467-022-28737-3
ISSN:2041-1723
An augmented reality microscope with real-time artificial intelligence integration for cancer diagnosis
Po-Hsuan Cameron Chen•Krishna Gadepalli•Robert MacDonald•Yun Liu•Shiro Kadowaki等 12 人
Nature Medicine
2019
•2019/8/12
•Vol.25 No.9 p.1453-1457
The microscopic assessment of tissue samples is instrumental for the diagnosis and staging of cancer, and thus guides therapy. However, these assessments demonstrate considerable variability and many regions of the world lack access to trained pathologists. Though artificial intelligence (AI) promis...
BiotechnologyEngineeringHealth care
10.1038/S41591-019-0539-7
ISSN:1078-8956
Regulatory T cells promote cancer immune-escape through integrin αvβ8-mediated TGF-β activation
Lainé Alexandra•Labiad Ossama•Hernandez-Vargas Hector•This Sébastien•Sanlaville Amélien等 11 人
Nature Communications
2021
•2021/10/28
•Vol.12 No.1 p.1-14
Presence of TGFβ in the tumor microenvironment is one of the most relevant cancer immune-escape mechanisms. TGFβ is secreted in an inactive form, and its activation within the tumor may depend on different cell types and mechanisms than its production. Here we show in mouse melanoma and breast cance...
Cancer microenvironmentImmunosuppressionLymphocyte differentiationTumour immunology
10.1038/S41467-021-26352-2
ISSN:2041-1723
Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells
Larionova Tatyana D.•Bastola Soniya•Aksinina Tatiana E.•Anufrieva Ksenia S.•Wang Jia等 26 人
Nature Cell Biology
2022
•2022/10/3
•Vol.24 No.10 p.1541-1557
Glioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alt...
Alternative splicingCNS cancerTumour heterogeneity
10.1038/S41556-022-00994-W
ISSN:1465-7392
Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes
Chirag Nepal•Jesper B. Andersen
Nature Communications
2023
•2023/5/11
•Vol.14 No.1 p.1-14
Transcriptional regulation is commonly governed by alternative promoters. However, the regulatory architecture in alternative and reference promoters, and how they differ, remains elusive. In 100 CAGE-seq libraries from hepatocellular carcinoma patients, here we annotate 4083 alternative promoters i...
Genome informaticsLiverLiver cancer
10.1038/S41467-023-38272-4
ISSN:2041-1723
Translational reprogramming marks adaptation to asparagine restriction in cancer
Gaurav Pathria•Joo Sang Lee•Erez Hasnis•Kristofferson Tandoc•David A. Scott等 12 人
Nature Cell Biology
2019
•2019/11/18
•Vol.21 No.12 p.1590-1603
While amino acid restriction remains an attractive strategy for cancer therapy, metabolic adaptations limit its effectiveness. Here we demonstrate a role of translational reprogramming in the survival of asparagine-restricted cancer cells. Asparagine limitation in melanoma and pancreatic cancer cell...
CancerCancer metabolismCell signallingTranslation
10.1038/S41556-019-0415-1
ISSN:1465-7392
Activated ATF6α is a hepatic tumour driver restricting immunosurveillance
Xin Li•Cynthia Lebeaupin•Aikaterini Kadianaki•Clementine Druelle-Cedano•Niklas Vesper等 98 人
Nature
2026
•2026/2/4
•Vol.651 No.8106 p.796-807
Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality and there are limited therapies1. Although endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR transducer ATF6α remains unclear2. Here&...
Cancer metabolismCancer therapyLiver cancer
10.1038/S41586-025-10036-8
ISSN:0028-0836
MEG8 as an antagonistic pleiotropic mechanism in breast cancer
Eva M. Verdugo-Sivianes•Asunción Espinosa-Sánchez•Ildefonso Cases•Ana M. Rojas•Daniel Otero-Albiol等 8 人
Cell Death Discovery
2024
•2024/12/20
•Vol.10 No.1 p.1-14
Cellular senescence connects aging and cancer. Cellular senescence is a common program activated by cells in response to various types of stress. During this process, cells lose their proliferative capacity and undergo distinct morphological and metabolic changes. Senescence itself constitutes a tum...
Breast cancerSenescence
10.1038/S41420-024-02272-0
ISSN:2058-7716
Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis
Zhou Xuantong•Huang Furong•Ma Gang•Wei Wenqing•Wu Nan等 6 人
Signal Transduction And Targeted Therapy
2022
•2022/10/24
•Vol.7 No.1 p.1-14
Whereas it is appreciated that cancer cells rewire lipid metabolism to survive and propagate, the roles of lipid metabolism in metastasis remain largely unknown. In this study, using esophageal squamous cell carcinoma (ESCC) as a pulmonary metastasis model, we find that the enzyme fatty acid 2-hydro...
Cancer metabolismDrug developmentGastrointestinal cancerMetastasisOncogenes
10.1038/S41392-022-01199-1
ISSN:2059-3635
A self-adaptive and versatile tool for eliminating multiple undesirable variations from large-scale transcriptomes
Mengji Zhang•Lei Yan•Xinbo Wang•Yi Yuan•Shimin Zou等 17 人
Nature Biomedical Engineering
2025
•2025/7/25
•00 p.1-14
Accurate identification of true biological signals from diverse undesirable variations in large-scale transcriptomes is essential for downstream discoveries. Here we develop a universal deep neural network, called DeepAdapter, to eliminate various undesirable variations including batch, platform, pu...
Data integrationData miningGene expression
10.1038/S41551-025-01466-W
ISSN:2157-846X
RFX2-BNIP3 axis-driven adaptive mitophagy promotes resistance to ACK1-targeted therapy in non-small cell lung cancer
Kui Cao•Shenshui Wei•Tianjiao Ma•Xiaolong Zou•Hongxue Meng等 11 人
Oncogene
2025
•2025/7/25
•00 p.1-15
Activated Cdc42-associated kinase 1 (ACK1) is an oncogenic non-receptor kinase that promotes tumor cell survival and impairs T-cell activation. Targeting ACK1 has great promise in cancer control. However, tumor adaptive responses that may limit the anticancer efficacy of ACK1 inhibition (ACK1i) rema...
Cancer geneticsCancer therapeutic resistance
10.1038/S41388-025-03502-0
ISSN:0950-9232
Targeting FSP1 triggers ferroptosis in lung cancer
Katherine Wu•Alec J. Vaughan•Jozef P. Bossowski•Yuan Hao•Aikaterini Ziogou等 20 人
Nature
2025
•2025/11/5
•00 p.1-9
Emerging evidence indicates that cancer cells are susceptible to ferroptosis, a form of cell death that is triggered by uncontrolled lipid peroxidation1–3. Despite broad enthusiasm about harnessing ferroptosis as a novel anti-cancer strategy, whether ferroptosis is a barrier to tumorigenesis and can...
Cancer modelsCell deathNon-small-cell lung cancer
10.1038/S41586-025-09710-8
ISSN:0028-0836
An IRAK1–PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy
Peter H. Liu•Richa B. Shah•Yuanyuan Li•Arshi Arora•Peter Man-Un Ung等 23 人
Nature Cell Biology
2019
•2019/1/21
•Vol.21 No.2 p.203-213
Drug-based strategies to overcome tumour resistance to radiotherapy (R-RT) remain limited by the single-agent toxicity of traditional radiosensitizers (for example, platinums) and a lack of targeted alternatives. In a screen for compounds that restore radiosensitivity in p53 mutant zebrafish while t...
CancerRadiotherapyStress signallingTargeted therapies
10.1038/S41556-018-0260-7
ISSN:1465-7392
Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment
Zhongyi Hu•Junzhi Zhou•Junjie Jiang•Jiao Yuan•Youyou Zhang等 19 人
Nature Communications
2019
•2019/2/13
•Vol.10 No.1 p.1-17
A growing emphasis in anticancer drug discovery efforts has been on targeting histone acetylation modulators. Here we comprehensively analyze the genomic alterations of the genes encoding histone acetylation modulator proteins (HAMPs) in the Cancer Genome Atlas cohort and observe that HAMPs have a h...
CancerCancer genomics
10.1038/S41467-019-08554-X
ISSN:2041-1723
Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity
Lam K. H. Brian•Leon Alberto J.•Hui Weili•Lee Sandy Che-Eun•Batruch Ihor等 12 人
Nature Communications
2022
•2022/1/10
•Vol.13 No.1 p.1-14
Glioblastoma is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance and progression. While regional and single cell transcriptomic variations of glioblastoma have been recently resolved, downstream phenotype-level proteo...
CancerCNS cancerMachine learningProteomicsTumour heterogeneity
10.1038/S41467-021-27667-W
ISSN:2041-1723
Pan-cancer circulating tumor DNA detection in over 10,000 Chinese patients
Yongliang Zhang•Yu Yao•Yaping Xu•Lifeng Li•Yan Gong等 13 人
Nature Communications
2021
•2021/1/4
•Vol.12 No.1 p.1-14
Circulating tumor DNA (ctDNA) provides a noninvasive approach to elucidate a patient’s genomic landscape and actionable information. Here, we design a ctDNA-based study of over 10,000 pan-cancer Chinese patients. Using parallel sequencing between plasma and white blood cells, 14% of plasma cell-free...
Cancer genomicsDNA sequencing
10.1038/S41467-020-20162-8
ISSN:2041-1723
A comprehensive proteogenomic pipeline for neoantigen discovery to advance personalized cancer immunotherapy
Florian Huber•Marion Arnaud•Brian J. Stevenson•Justine Michaux•Fabrizio Benedetti等 29 人
Nature Biotechnology
2024
•2024/10/11
•00 p.1-13
The accurate identification and prioritization of antigenic peptides is crucial for the development of personalized cancer immunotherapies. Publicly available pipelines to predict clinical neoantigens do not allow direct integration of mass spectrometry immunopeptidomics data, which can uncover anti...
ImmunizationMHCTumour immunology
10.1038/S41587-024-02420-Y
ISSN:1087-0156
GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating RAC2 GTPase
Yutong Chen•Weiyu Zhang•Yan Zeng•Pengfei Yang•Yaning Li等 15 人
Oncogene
2024
•2024/7/17
•00 p.1-14
Perineural invasion (PNI) is an adverse prognostic feature of pancreatic ductal adenocarcinoma (PDAC). However, the understanding of the interactions between tumors and neural signaling within the tumor microenvironment is limited. In the present study, we found that MUC21 servers as an independent ...
OncogenesPancreatic cancerPrognostic markersRHO signalling
10.1038/S41388-024-03102-4
ISSN:0950-9232
Targeting spermine metabolism to overcome immunotherapy resistance in pancreatic cancer
Hanshen Yang•Xiaozhen Zhang•Sirui Zhang•Yanqing Yang•Yan Chen等 22 人
Nature Communications
2025
•2025/8/22
•Vol.16 No.1 p.1-19
While dysregulation of polyamine metabolism is frequently observed in cancer, it is unknown how polyamines alter the tumor microenvironment (TME) and contribute to therapeutic resistance. Analysis of polyamines in the plasma of pancreatic cancer patients reveals that spermine levels are significantl...
Cancer immunotherapyCancer metabolismPancreatic cancer
10.1038/S41467-025-63146-2
ISSN:2041-1723
Human melanocyte development and melanoma dedifferentiation at single-cell resolution
Belote Rachel L.•Le Daniel•Maynard Ashley•Lang Ursula E.•Sinclair Adriane等 11 人
Nature Cell Biology
2021
•2021/9/2
•00 p.1-13
In humans, epidermal melanocytes are responsible for skin pigmentation, defence against ultraviolet radiation and the deadliest common skin cancer, melanoma. Although there is substantial overlap in melanocyte development pathways between different model organisms, species-dependent differences are ...
DifferentiationMelanomaRNA sequencingTumour heterogeneity
10.1038/S41556-021-00740-8
ISSN:1465-7392
Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma
Najla El-Hachem•Marine Leclercq•Miguel Susaeta Ruiz•Raphael Vanleyssem•Kateryna Shostak等 23 人
Nature Cell Biology
2024
•2024/6/7
•00 p.1-11
Transfer RNA dynamics contribute to cancer development through regulation of codon-specific messenger RNA translation. Specific aminoacyl-tRNA synthetases can either promote or suppress tumourigenesis. Here we show that valine aminoacyl-tRNA synthetase (VARS) is a key player in the codon-biased tran...
MelanomaTargeted therapiesTranslation
10.1038/S41556-024-01439-2
ISSN:1465-7392
PTENα and PTENβ promote carcinogenesis through WDR5 and H3K4 trimethylation
Shao-Ming Shen•Cheng Zhang•Meng-Kai Ge•Shuang-Shu Dong•Li Xia等 14 人
Nature Cell Biology
2019
•2019/11/4
•Vol.21 No.11 p.1436-1448
PTENα and PTENβ are two longer translational variants of phosphatase and tensin homolog (PTEN) messenger RNA. Their expressional regulations and functions in carcinogenesis remain largely unknown. Here, we demonstrate that, in contrast with the well-established tumour-suppressive role of canonical P...
CancerCancer genomicsTumour-suppressor proteinsUbiquitylation
10.1038/S41556-019-0409-Z
ISSN:1465-7392
Nucleolar protein NOC4L inhibits tumorigenesis and progression by attenuating SIRT1-mediated p53 deacetylation
Jia Xiaomeng•Liu Huijiao•Ren Xinmin•Li Peng•Song Runjie等 8 人
Oncogene
2022
•2022/8/27
•Vol.41 No.39 p.4474-4484
SIRT1 is an NAD+-dependent deacetylase and plays an important role in the deacetylation of both histone and non-histone proteins. Many studies revealed that SIRT1 is upregulated in a variety of tumors and tightly associated with tumorigenesis and cancer progression, but the detailed underlying mecha...
OncogenesPrognostic markers
10.1038/S41388-022-02447-Y
ISSN:0950-9232
Non-muscle-invasive micropapillary bladder cancer has a distinct lncRNA profile associated with unfavorable prognosis
de Jong Joep J.•Valderrama Begoña P.•Perera Julia•Juanpere Nuria•Cejas Paloma等 9 人
British Journal Of Cancer
2022
•2022/4/21
•00 p.1-8
Molecular subtyping of bladder cancer has revealed luminal tumors generally have a more favourable prognosis. However, some aggressive forms of variant histology, including micropapillary, are often classified luminal. In previous work, we found long non-coding RNA (lncRNA) expression profiles could...
Bladder cancerDiagnostic markers
10.1038/S41416-022-01799-2
ISSN:0007-0920
Predicting tumour mutational burden from histopathological images using multiscale deep learning
Mika S. Jain•Tarik F. Massoud
Nature Machine Intelligence
2020
•2020/6/15
•Vol.2 No.6 p.356-362
Tumour mutational burden (TMB) is an important biomarker for predicting the response to immunotherapy in patients with cancer. Gold-standard measurement of TMB is performed using whole exome sequencing (WES), which is not available at most hospitals because of its high cost, operational complexity a...
BiomarkersCancerComputational biology and bioinformaticsDiseasesImmunology
10.1038/S42256-020-0190-5
ISSN:2522-5839
Integrative single-cell analysis of human colorectal cancer reveals patient stratification with distinct immune evasion mechanisms
Xiaojing Chu•Xiangjie Li•Yu Zhang•Guohui Dang•Yuhui Miao等 9 人
Nature Cancer
2024
•2024/8/15
•00 p.1-18
The tumor microenvironment (TME) considerably influences colorectal cancer (CRC) progression, therapeutic response and clinical outcome, but studies of interindividual heterogeneities of the TME in CRC are lacking. Here, by integrating human colorectal single-cell transcriptomic data from approximat...
CancerColorectal cancerData integrationImmunosurveillance
10.1038/S43018-024-00807-Z
ISSN:2662-1347
Targeting SPAK suppresses progression and averts an immune exhaustive microenvironment in hepatocellular carcinoma
Yonglong Pan•Chenglong Zeng•Yi He•Ruizhi Chang•Jingjing Wu等 22 人
Nature Communications
2026
•2026/1/12
•Vol.17 No.1 p.14140
Protein kinases contribute to hepatocellular carcinoma (HCC) development and immune evasion, posing major challenges for HCC management. Here we show STE20/SPS1-related proline/alanine-rich kinase (SPAK) as a candidate immune exhaustion–associated gene identified through a pooled screen of protein k...
OncologyPhosphorylationTumour biomarkers
10.1038/S41467-025-68156-8
ISSN:2041-1723
Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma
Ombretta Melaiu•Marco Chierici•Valeria Lucarini•Giuseppe Jurman•Libenzio Adrian Conti等 13 人
Nature Communications
2020
•2020/11/25
•Vol.11 No.1 p.1-15
Tumor-infiltrating lymphocytes play an essential role in improving clinical outcome of neuroblastoma (NB) patients, but their relationship with other tumor-infiltrating immune cells in the T cell-inflamed tumors remains poorly investigated. Here we show that dendritic cells (DCs) and natural killer ...
Cancer microenvironmentDendritic cellsNK cellsPaediatric cancer
10.1038/S41467-020-19781-Y
ISSN:2041-1723
Open and reusable deep learning for pathology with WSInfer and QuPath
Jakub R. Kaczmarzyk•Alan O’Callaghan•Fiona Inglis•Swarad Gat•Tahsin Kurc等 9 人
Npj Precision Oncology
2024
•2024/1/10
•Vol.8 No.1 p.1-5
Digital pathology has seen a proliferation of deep learning models in recent years, but many models are not readily reusable. To address this challenge, we developed WSInfer: an open-source software ecosystem designed to streamline the sharing and reuse of deep learning models for digital pathology....
Cancer imagingComputational biology and bioinformatics
10.1038/S41698-024-00499-9
ISSN:2397-768X
Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery
Bohong Chen•Tianyu Ge•Meiqi Jian•Liutao Chen•Zhengwen Fang等 17 人
Nature Cell Biology
2023
•2023/6/15
•00 p.1-13
Proper repair of DNA damage lesions is essential to maintaining genome integrity and preventing the development of human diseases, including cancer. Increasing evidence suggests the importance of the nuclear envelope in the spatial regulation of DNA repair, although the mechanisms of such regulatory...
Cancer therapeutic resistanceNon-homologous-end joining
10.1038/S41556-023-01165-1
ISSN:1465-7392
Dual therapeutic targeting of MYC and JUNB transcriptional programs for enhanced anti-myeloma activity
Judith Lind•Osman Aksoy•Michaela Prchal-Murphy•Fengjuan Fan•Mariateresa Fulciniti等 13 人
Blood Cancer Journal
2024
•2024/8/19
•Vol.14 No.1 p.1-12
Deregulation of transcription factors (TFs) leading to uncontrolled proliferation of tumor cells within the microenvironment represents a hallmark of cancer. However, the biological and clinical impact of transcriptional interference, particularly in multiple myeloma (MM) cells, remains poorly under...
Haematological cancerPathogenesis
10.1038/S41408-024-01117-4
ISSN:2044-5385
Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis
Jun Nishida•Yusaku Momoi•Kosuke Miyakuni•Yusuke Tamura•Kei Takahashi等 8 人
Nature Cell Biology
2020
•2020/3/23
•Vol.22 No.4 p.465-475
Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Recent studies have shown that cancer cells reshape the immune landscape by secreting cytokines or chemokines. This phenotype, called cancer-cell-intrinsic inflammation, triggers a metastatic cascade. Here, we ...
Cancer epigeneticsInflammationMetastasisRenal cancer
10.1038/S41556-020-0491-2
ISSN:1465-7392
Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments
Michalina Janiszewska•Doris P. Tabassum•Zafira Castaño•Simona Cristea•Kimiyo N. Yamamoto等 24 人
Nature Cell Biology
2019
•2019/7/1
•Vol.21 No.7 p.879-888
Most human tumours are heterogeneous, composed of cellular clones with different properties present at variable frequencies. Highly heterogeneous tumours have poor clinical outcomes, yet the underlying mechanism remains poorly understood. Here, we show that minor subclones of breast cancer cells exp...
CancerCancer microenvironmentMetastasisTumour heterogeneityTumour immunology
10.1038/S41556-019-0346-X
ISSN:1465-7392
Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma
Dan Liao•Li Zhong•Junqiang Yin•Cuiling Zeng•Xin Wang等 18 人
Nature Cell Biology
2020
•2020/6/1
•Vol.22 No.7 p.868-881
Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon–intron fusion genes in osteosarcoma cell lines and tissu...
Bone cancerCancerCancer therapyMetastasis
10.1038/S41556-020-0522-Z
ISSN:1465-7392
5-methylcytosine and 5-hydroxymethylcytosine are synergistic biomarkers for early detection of colorectal cancer
Fabio Puddu•Annelie Johansson•Aurélie Modat•Jamie Scotcher•Riccha Sethi等 17 人
Communications Medicine
2026
•2026/1/20
•Vol.6 No.1 p.150
Early cancer detection has the potential to significantly improve treatment outcomes and survival rates. This study investigates the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA). We analyze...
CancerGastrointestinal cancer
10.1038/S43856-025-01278-8
ISSN:2730-664X
Upregulated PrPC by HBx enhances NF-κB signal via liquid–liquid phase separation to advance liver cancer
Yang Liu•Jing Zhang•Zixu Zhai•Chenyi Liu•Siqi Yang等 16 人
Npj Precision Oncology
2024
•2024/9/27
•Vol.8 No.1 p.1-21
Cellular prion protein (PrPC) has been implicated in carcinogenic through the activation of various signal pathways, however, the precise mechanisms remain elusive. In vitro studies have shown that PrPC is prone to undergo liquid-liquid phase separation (LLPS). However, it remains unknown whether Pr...
Growth factor signallingHepatocellular carcinomaMolecular biology
10.1038/S41698-024-00697-5
ISSN:2397-768X
MLL3 loss drives metastasis by promoting a hybrid epithelial–mesenchymal transition state
Cui Jihong•Zhang Chi•Lee Ji-Eun•Bartholdy Boris A.•Yang Dapeng等 13 人
Nature Cell Biology
2023
•2023/1/5
•Vol.25 No.1 p.145-158
Phenotypic plasticity associated with the hybrid epithelial–mesenchymal transition (EMT) is crucial to metastatic seeding and outgrowth. However, the mechanisms governing the hybrid EMT state remain poorly defined. Here we showed that deletion of the epigenetic regulator MLL3, a tumour suppressor fr...
Breast cancerCancer epigeneticsEpithelial–mesenchymal transitionMetastasis
10.1038/S41556-022-01045-0
ISSN:1465-7392
Deciphering the cellular and molecular landscape of cervical cancer progression through single-cell and spatial transcriptomics
Peng Xia•Juanhong Zhou•Rong Shen•Degui Wang
Npj Precision Oncology
2025
•2025/5/28
•Vol.9 No.1 p.1-14
Cervical cancer represents a significant global health challenge, with complex cellular and molecular mechanisms driving its progression from HPV infection to invasive malignancy. This study employed an integrated approach combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics ...
Cervical cancerRisk factorsTumour heterogeneity
10.1038/S41698-025-00948-Z
ISSN:2397-768X
The proteasome regulator PSME4 modulates proteasome activity and antigen diversity to abrogate antitumor immunity in NSCLC
Aaron Javitt•Merav D. Shmueli•Matthias P. Kramer•Aleksandra A. Kolodziejczyk•Ivan J. Cohen等 30 人
Nature Cancer
2023
•2023/5/22
•Vol.4 No.5 p.629-647
Immunotherapy revolutionized treatment options in cancer, yet the mechanisms underlying resistance in many patients remain poorly understood. Cellular proteasomes have been implicated in modulating antitumor immunity by regulating antigen processing, antigen presentation, inflammatory signaling and ...
CancerImmunosurveillanceMHC class INon-small-cell lung cancerProteasome
10.1038/S43018-023-00557-4
ISSN:2662-1347
Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1–HER3 signaling
Roberto Würth•Elisa Donato•Laura L. Michel•Massimo Saini•Lisa Becker等 42 人
Nature Cancer
2025
•2025/1/3
•00 p.1-19
Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establi...
Breast cancerCancerCancer modelsMechanisms of disease
10.1038/S43018-024-00882-2
ISSN:2662-1347
Antisense oligonucleotides targeting lncRNA AC104041.1 induces antitumor activity through Wnt2B/β-catenin pathway in head and neck squamous cell carcinomas
Mengwei Li•Xu Ding•Yinan Zhang•Xin Li•Haoze Zhou等 13 人
Cell Death & Disease
2020
•2020/8/13
•Vol.11 No.8 p.1-12
Long non-coding RNAs (lncRNAs) contribute to the initiation and progression of various tumors, including head and neck squamous carcinoma (HNSCC), which is a common malignancy with high morbidity and low survival rate. However, the mechanism of lncRNAs in HNSCC tumorigenesis remains largely unexplor...
Head and neck cancerTargeted therapies
10.1038/S41419-020-02820-3
ISSN:2041-4889
AI powered quantification of nuclear morphology in cancers enables prediction of genome instability and prognosis
John Abel•Suyog Jain•Deepta Rajan•Harshith Padigela•Kenneth Leidal等 27 人
Npj Precision Oncology
2024
•2024/6/19
•Vol.8 No.1 p.1-14
While alterations in nucleus size, shape, and color are ubiquitous in cancer, comprehensive quantification of nuclear morphology across a whole-slide histologic image remains a challenge. Here, we describe the development of a pan-tissue, deep learning-based digital pathology pipeline for exhaustive...
CancerComputational biology and bioinformatics
10.1038/S41698-024-00623-9
ISSN:2397-768X
Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
Junyi Xin•Dongying Gu•Shuwei Li•Sangni Qian•Yifei Cheng等 16 人
Nature Communications
2024
•2024/4/8
•Vol.15 No.1 p.1-11
The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a ge...
Cancer epidemiologyGenetic association studyPrognostic markers
10.1038/S41467-024-47204-9
ISSN:2041-1723
Classification and mutation prediction from non–small cell lung cancer histopathology images using deep learning
Nicolas Coudray•Paolo Santiago Ocampo•Theodore Sakellaropoulos•Navneet Narula•Matija Snuderl等 9 人
Nature Medicine
2018
•2018/9/17
•Vol.24 No.10 p.1559-1567
Visual inspection of histopathology slides is one of the main methods used by pathologists to assess the stage, type and subtype of lung tumors. Adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the most prevalent subtypes of lung cancer, and their distinction requires visual inspection b...
Machine learning
10.1038/S41591-018-0177-5
ISSN:1078-8956
Machine learning algorithms for predicting glioma patient prognosis based on CD163+FPR3+ macrophage signature
Quanwei Zhou•Xuejun Yan•Youwei Guo•Xingjun Jiang•Tuo Cao等 6 人
Npj Precision Oncology
2024
•2024/9/13
•Vol.8 No.1 p.1-12
Tumor-associated macrophages (TAMs) play a vital role in glioma progression and are associated with poor outcomes in glioma patients. However, the specific roles of different subpopulations of TAMs remain poorly understood. Two distinct cell types, glioma and myeloid cells, were identified through s...
CNS cancerSurgical oncology
10.1038/S41698-024-00692-W
ISSN:2397-768X
Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation
Georgios Kanellos•Chiara Giacomelli•Alexander Raven•Nikola Vlahov•Hu Jin等 33 人
Nature Genetics
2025
•2025/12/18
•00 p.1-16
Nucleophosmin (NPM1), a nucleolar protein frequently mutated in hematopoietic malignancies, is overexpressed in several solid tumors with poorly understood functional roles. Here, we demonstrate that Npm1 is upregulated after APC loss in WNT-responsive tissues and supports WNT-driven intestinal and ...
Colorectal cancerGene regulationLiver cancerTumour biomarkers
10.1038/S41588-025-02408-7
ISSN:1061-4036
Intermittent fasting inhibits Tp53-driven glioma through gut microbiota-mediated methionine-m6A regulation
Yao Lin•ShihJung Li•Xinyue Xu•Xiaopeng Hu•Yueqi Li等 20 人
Nature Communications
2026
•2026/1/20
•Vol.17 No.1 p.18040
Intermittent fasting (IF) has emerged as a potential cancer treatment modality, although its tumor-suppressive effects are limited. Glioblastoma (GBM) can be classified into CDKN2A subtype and TP53 subtype. Here, we discover that the efficacy of IF is correlated with tumor subtypes of GBM. IF signif...
Bacterial host responseCancer metabolismTranscriptomics
10.1038/S41467-026-68512-2
ISSN:2041-1723
Deep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer
Cristian Barrera•Germán Corredor•Vidya Sankar Viswanathan•Ruiwen Ding•Paula Toro等 21 人
Npj Precision Oncology
2023
•2023/6/1
•Vol.7 No.1 p.1-17
The tumor immune composition influences prognosis and treatment sensitivity in lung cancer. The presence of effective adaptive immune responses is associated with increased clinical benefit after immune checkpoint blockers. Conversely, immunotherapy resistance can occur as a consequence of local T-c...
Cancer imagingCancer microenvironmentMathematics and computingPrognostic markers
10.1038/S41698-023-00403-X
ISSN:2397-768X
NASH limits anti-tumour surveillance in immunotherapy-treated HCC
Dominik Pfister•Nicolás Gonzalo Núñez•Roser Pinyol•Olivier Govaere•Matthias Pinter等 110 人
Nature
2021
•2021/3/24
•00 p.1-8
Hepatocellular carcinoma (HCC) can have viral or non-viral causes1–5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we repo...
CancerImmunotherapy
10.1038/S41586-021-03362-0
ISSN:0028-0836
Identifying the crucial oncogenic mechanisms of DDX56 based on a machine learning-based integration model of RNA-binding proteins
Hui Jiang•Haotian Zheng•Xinjie Zhao•Yunzhi Xiang•Jiahao Li等 8 人
Npj Precision Oncology
2025
•2025/7/17
•Vol.9 No.1 p.1-19
RNA-binding proteins (RBPs) play a fundamental role in cellular metabolism, with their disturbance leading to large-scale transcriptomic dysregulation. RBP dysregulation is highly prevalent in human cancers; however, its role in lung adenocarcinoma (LUAD) has not been systematically investigated. To...
BiomarkersCancerComputational biology and bioinformaticsImmunologyOncology
10.1038/S41698-025-01039-9
ISSN:2397-768X
NRF2 mediates melanoma addiction to GCDH by modulating apoptotic signalling
Verma Sachin•Crawford David•Khateb Ali•Feng Yongmei•Sergienko Eduard等 13 人
Nature Cell Biology
2022
•2022/9/1
•Vol.24 No.9 p.1422-1432
Tumour dependency on specific metabolic signals has been demonstrated and often guided numerous therapeutic approaches. We identify melanoma addiction to the mitochondrial protein glutaryl-CoA dehydrogenase (GCDH), which functions in lysine metabolism and controls protein glutarylation. GCDH knockdo...
ApoptosisCancer metabolismMelanomaStress signalling
10.1038/S41556-022-00985-X
ISSN:1465-7392
The involvement of lncRNA EMSLR in the disulfidptosis and progression of endometrial carcinoma
Yixuan Sun•Ruiwen Wang•Xinzhu Li•Wanzhen Zhou•Huixian Huang等 9 人
Cancer Gene Therapy
2025
•2025/8/14
•Vol.32 No.10 p.1107-1119
The incidence of endometrial cancer (EC) continues to rise. Disulfidptosis, a novel form of cell death, may represent a potential therapeutic target in EC. Through bioinformatic analysis of The Cancer Genome Atlas (TCGA) database, E2F1 mRNA-stabilizing lncRNA (EMSLR) was identified as a lncRNA relat...
BiomarkersEndometrial cancer
10.1038/S41417-025-00918-4
ISSN:0929-1903
Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
Valeria Capaci•Lorenzo Bascetta•Marco Fantuz•Galina V. Beznoussenko•Roberta Sommaggio等 24 人
Nature Communications
2020
•2020/8/7
•Vol.11 No.1 p.1-19
TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify struct...
Cancer microenvironmentGolgiMetastasisOncogenesSuper-resolution microscopy
10.1038/S41467-020-17596-5
ISSN:2041-1723
Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity
Haojie Dong•Xin He•Lei Zhang•Wei Chen•Yi-Chun Lin等 32 人
Nature Cancer
2024
•2024/2/27
•00 p.1-24
Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia st...
CancerTumour immunology
10.1038/S43018-024-00736-X
ISSN:2662-1347
PAK4 inhibition improves PD-1 blockade immunotherapy
Gabriel Abril-Rodriguez•Davis Y. Torrejon•Wei Liu•Jesse M. Zaretsky•Theodore S. Nowicki等 21 人
Nature Cancer
2019
•2019/12/9
•Vol.1 No.1 p.46-58
Lack of tumor infiltration by immune cells is the main mechanism of primary resistance to programmed cell death protein 1 (PD-1) blockade therapies for cancer. It has been postulated that cancer cell-intrinsic mechanisms may actively exclude T cells from tumors, suggesting that the finding of action...
Cancer immunotherapyCancer therapeutic resistanceSkin cancerTumour immunology
10.1038/S43018-019-0003-0
ISSN:2662-1347
Glucocorticoid receptor regulates PD-L1 and MHC-I in pancreatic cancer cells to promote immune evasion and immunotherapy resistance
Deng Yalan•Xia Xianghou•Zhao Yang•Zhao Zilong•Martinez Consuelo等 18 人
Nature Communications
2021
•2021/12/6
•Vol.12 No.1 p.1-16
Despite unprecedented responses of some cancers to immune checkpoint blockade (ICB) therapies, the application of checkpoint inhibitors in pancreatic cancer has been unsuccessful. Glucocorticoids and glucocorticoid receptor (GR) signaling are long thought to suppress immunity by acting on immune cel...
Cancer immunotherapyPancreatic cancer
10.1038/S41467-021-27349-7
ISSN:2041-1723
VDAC2 loss elicits tumour destruction and inflammation for cancer therapy
Sujing Yuan•Renqiang Sun•Hao Shi•Nicole M. Chapman•Haoran Hu等 15 人
Nature
2025
•2025/3/19
•00 p.1-10
Tumour cells often evade immune pressure exerted by CD8+ T cells or immunotherapies through mechanisms that are largely unclear1,2. Here, using complementary in vivo and in vitro CRISPR–Cas9 genetic screens to target metabolic factors, we established voltage-dependent anion channel 2 (VDAC2) as an i...
Cytotoxic T cellsImmune evasionInterferons
10.1038/S41586-025-08732-6
ISSN:0028-0836
AKT/mTOR as a targetable hub to overcome multimodal resistance to EGFR inhibitors in oesophageal squamous cell carcinoma
Lindsay C. Spender•Dale M. Watt•Mark A. Baxter•Morven K. Shuttleworth•Kateah Walker等 15 人
British Journal Of Cancer
2025
•2025/7/4
•00 p.1-14
Oesophageal squamous cell carcinoma (ESCC) is associated with late-stage diagnosis, limited treatment options, the development of drug resistance and poor outcome. Epidermal growth factor receptor is frequently dysregulated in ESCC. EGFR copy number gain and/or protein overexpression are beneficial ...
Oesophageal cancer
10.1038/S41416-025-03093-3
ISSN:0007-0920
IL-10 in glioma
Widodo Samuel S.•Dinevska Marija•Furst Liam M.•Stylli Stanley S.•Mantamadiotis Theo
British Journal Of Cancer
2021
•2021/8/4
•00 p.1-11
The prognosis for patients with glioblastoma (GBM), the most common and malignant type of primary brain tumour, is very poor, despite current standard treatments such as surgery, radiotherapy and chemotherapy. Moreover, the immunosuppressive tumour microenvironment hinders the development of effecti...
CNS cancerTumour immunology
10.1038/S41416-021-01515-6
ISSN:0007-0920
Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2–SP1–SAT1 axis
Divya Murthy•Kuldeep S. Attri•Surendra K. Shukla•Ravi Thakur•Nina V. Chaika等 37 人
Nature Cell Biology
2024
•2024/3/1
•00 p.1-15
The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP ...
Cancer metabolismCancer microenvironmentPancreatic cancer
10.1038/S41556-024-01372-4
ISSN:1465-7392
Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development
Sangkyeong Eom•Jongjin Peak•Jongyeun Park•Seung Hyun Ahn•You Kyung Cho等 19 人
Nature Cell Biology
2023
•2023/9/7
•Vol.25 No.9 p.1369-1383
Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o8G) can change RNA–RNA interactions via o8G•A base pairing, but its regulatory roles remain elusive. Here, on the basis of o8G-induced guanine-to-thymine (o8G > T) variations ...
EpigenomicsHepatocellular carcinomamiRNAs
10.1038/S41556-023-01209-6
ISSN:1465-7392
ImmuneLENS characterizes systemic immune dysregulation in aging and cancer
Robert Bentham•Thomas P. Jones•James R. M. Black•Carlos Martinez-Ruiz•Michelle Dietzen等 14 人
Nature Genetics
2025
•2025/2/18
•Vol.57 No.3 p.694-705
Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fraction...
DNA sequencingGenetics researchSoftwareTumour immunology
10.1038/S41588-025-02086-5
ISSN:1061-4036
Detecting and understanding meaningful cancerous mutations based on computational models of mRNA splicing
Nicolas Lynn•Tamir Tuller
Npj Systems Biology And Applications
2024
•2024/3/7
•Vol.10 No.1 p.1-15
Cancer research has long relied on non-silent mutations. Yet, it has become overwhelmingly clear that silent mutations can affect gene expression and cancer cell fitness. One fundamental mechanism that apparently silent mutations can severely disrupt is alternative splicing. Here we introduce Oncosp...
Computational biology and bioinformaticsGeneticsMolecular medicine
10.1038/S41540-024-00351-7
ISSN:2056-7189
Self-amplifying NRF2–EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer
Laura Antonucci•Na Li•Angeles Duran•Isidoro Cobo•Chiara Nicoletti等 42 人
Nature Cancer
2025
•2025/6/30
•00 p.1-20
Pancreatic ductal adenocarcinoma (PDAC) emerges from mutant KRAS-harboring but dormant low-grade pancreatic intraepithelial neoplasia (PanIN). To examine the role of oxidative stress, a putative PDAC risk factor, we established an organoid-based transformation system. Although the prototypic oxidant...
CancerPancreatic cancerStress signalling
10.1038/S43018-025-01003-3
ISSN:2662-1347
Tumor-associated macrophages-induced lncRNA RP11-627G18.1 promotes breast cancer metastasis
Luna Hong•Yijiao Huang•Fengzhan Ye•Shan Wang•Yongqiang Wang等 10 人
Genes & Immunity
2025
•2025/6/9
•00 p.1-13
Tumor-associated macrophages (TAMs) promote the transition of breast cancer cells from an epithelioid to a mesenchymal phenotype (EMT) and facilitate breast cancer metastasis, but the role of lncRNA in this process is poorly understood. We employed bioinformatics analysis to identify TAMs-related ln...
ImmunosurveillanceMonocytes and macrophages
10.1038/S41435-025-00339-1
ISSN:1476-5470
Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast
Xuguang Liu•Xin Huang•Yan Bai•Zhiwen Zhang•Tiefeng Jin等 7 人
Npj Precision Oncology
2021
•2021/5/18
•Vol.5 No.1 p.1-9
Encapsulated papillary carcinoma (EPC) of the breast is a rare subtype of tumor. To date, the genetic abnormalities underlying EPC remain elusive. The purpose of this study was to gain further insight into EPC mutation profile. Forty-one EPCs diagnosed from 2015 to 2018 were included. Twenty-six EPC...
Breast cancerOncogenesis
10.1038/S41698-021-00180-5
ISSN:2397-768X
ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages
Jinlong Yin•Sung Soo Kim•Eunji Choi•Young Taek Oh•Weiwei Lin等 24 人
Nature Communications
2020
•2020/6/12
•Vol.11 No.1 p.1-15
The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arse...
Cancer stem cellsCNS cancer
10.1038/S41467-020-16789-2
ISSN:2041-1723
The gut microbial metabolite formate exacerbates colorectal cancer progression
Ternes Dominik•Tsenkova Mina•Pozdeev Vitaly Igorevich•Meyers Marianne•Koncina Eric等 31 人
Nature Metabolism
2022
•2022/4/18
•00 p.1-18
The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains larg...
Bacterial host responseCancer metabolismColorectal cancerMetabolism
10.1038/S42255-022-00558-0
ISSN:2522-5812
The pancancer overexpressed NFYC Antisense 1 controls cell cycle mitotic progression through in cis and in trans modes of action
Cecilia Pandini•Giulia Pagani•Martina Tassinari•Emanuele Vitale•Eugenia Bezzecchi等 12 人
Cell Death & Disease
2024
•2024/3/11
•Vol.15 No.3 p.1-14
Antisense RNAs (asRNAs) represent an underappreciated yet crucial layer of gene expression regulation. Generally thought to modulate their sense genes in cis through sequence complementarity or their act of transcription, asRNAs can also regulate different molecular targets in trans, in the nucleus ...
Long non-coding RNAsNon-small-cell lung cancerSmall-cell lung cancer
10.1038/S41419-024-06576-Y
ISSN:2041-4889
Multi-resolution deep learning characterizes tertiary lymphoid structures and their prognostic relevance in solid tumors
Mart van Rijthoven•Simon Obahor•Fabio Pagliarulo•Maries van den Broek•Peter Schraml等 9 人
Communications Medicine
2024
•2024/1/5
•Vol.4 No.1 p.1-14
Tertiary lymphoid structures (TLSs) are dense accumulations of lymphocytes in inflamed peripheral tissues, including cancer, and are associated with improved survival and response to immunotherapy in various solid tumors. Histological TLS quantification has been proposed as a novel predictive and pr...
LymphocytesPrognostic markersTumour immunology
10.1038/S43856-023-00421-7
ISSN:2730-664X
Pan-cancer clinical impact of latent drivers from double mutations
Yavuz Bengi Ruken•Tsai Chung-Jung•Nussinov Ruth•Tuncbag Nurcan
Communications Biology
2023
•2023/2/20
•Vol.6 No.1 p.1-14
Here, we discover potential ‘latent driver’ mutations in cancer genomes. Latent drivers have low frequencies and minor observable translational potential. As such, to date they have escaped identification. Their discovery is important, since when paired in cis, latent driver mutations can drive canc...
CancerComputational biology and bioinformatics
10.1038/S42003-023-04519-5
ISSN:2399-3642
EGFR inhibition triggers an adaptive response by co-opting antiviral signaling pathways in lung cancer
Ke Gong•Gao Guo•Nishah Panchani•Matthew E. Bender•David E. Gerber等 20 人
Nature Cancer
2020
•2020/4/6
•Vol.1 No.4 p.394-409
EGFR inhibition is an effective treatment in the minority of non-small cell lung cancer (NSCLC) cases harboring EGFR-activating mutations, but not in EGFR wild-type (EGFRwt) tumors. Here we demonstrate that EGFR inhibition triggers an antiviral defense pathway in NSCLC. Inhibiting mutant EGFR trigge...
Cancer therapeutic resistanceCell signallingNon-small-cell lung cancerPreclinical researchPrognostic markers
10.1038/S43018-020-0048-0
ISSN:2662-1347
Highly aneuploid non-small cell lung cancer shows enhanced responsiveness to concurrent radiation and immune checkpoint blockade
Spurr Liam F.•Martinez Carlos A.•Kang Wenjun•Chen Mengjie•Zha Yuanyuan等 22 人
Nature Cancer
2022
•2022/11/28
•Vol.3 No.12 p.1498-1512
Over 500 clinical trials are investigating combination radiotherapy and immune checkpoint blockade (ICB) as cancer treatments; however, the majority of trials have found no positive interaction. Here we perform a comprehensive molecular analysis of a randomized phase I clinical trial of patients wit...
CancerCancer genomicsImmunotherapyNon-small-cell lung cancerRadiotherapy
10.1038/S43018-022-00467-X
ISSN:2662-1347
Hepatocytes functionally reprogrammed by KIAA1199-high colorectal cancer cells favour the accumulation of pro-metastatic Egr1+ neutrophils
Lisha Li•Lei Zhao•Kui Cao•Peiyi Zhang•Guojie Xu等 13 人
Nature Communications
2026
•2026/2/7
•Vol.17 No.1 p.24620
Colorectal cancer liver metastasis (CRLM) is a leading cause of mortality, driven by poorly defined molecular interactions within the hepatic niche. Here, we identify a distinct population of pro-metastatic Early Growth Response 1 (Egr1)+ neutrophils that accumulate in the pre-metastatic liver. Mech...
Gene regulation in immune cellsSignal transductionTumour immunology
10.1038/S41467-026-69250-1
ISSN:2041-1723
Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
Chaitanya Erady•Adam Boxall•Shraddha Puntambekar•N. Suhas Jagannathan•Ruchi Chauhan等 17 人
Npj Genomic Medicine
2021
•2021/1/25
•Vol.6 No.1 p.1-17
Uncharacterized and unannotated open-reading frames, which we refer to as novel open reading frames (nORFs), may sometimes encode peptides that remain unexplored for novel therapeutic opportunities. To our knowledge, no systematic identification and characterization of transcripts encoding nORFs or ...
GeneticsSystems biology
10.1038/S41525-020-00167-4
ISSN:2056-7944
Gasdermin E mediates resistance of pancreatic adenocarcinoma to enzymatic digestion through a YBX1–mucin pathway
Lv Jiadi•Liu Yuying•Mo Siqi•Zhou Yabo•Chen Fengye等 16 人
Nature Cell Biology
2022
•2022/3/15
•Vol.24 No.3 p.364-372
Pancreatic ductal adenocarcinoma (PDAC) originates from normal pancreatic ducts where digestive juice is regularly produced. It remains unclear how PDAC can escape autodigestion by digestive enzymes. Here we show that human PDAC tumour cells use gasdermin E (GSDME), a pore-forming protein, to mediat...
GlycoproteinsMechanisms of diseasePancreatic cancer
10.1038/S41556-022-00857-4
ISSN:1465-7392
Evaluating cancer etiology and risk with a mathematical model of tumor evolution
Pénisson Sophie•Lambert Amaury•Tomasetti Cristian
Nature Communications
2022
•2022/11/24
•Vol.13 No.1 p.1-11
Recent evidence arising from DNA sequencing of healthy human tissues has clearly indicated that our organs accumulate a relevant number of somatic mutations due to normal endogenous mutational processes, in addition to those caused by environmental factors. A deeper understanding of the evolution of...
Cancer epidemiologyCancer genomicsCancer modelsCancer preventionComputational models
10.1038/S41467-022-34760-1
ISSN:2041-1723
A full-automated tumor budding annotation approach in hematoxylin and eosin-stained whole slide images of colorectal cancer
Song Peng•Xiaona Chang•Yuehao Luo•He Tang•Ming Yang等 12 人
Npj Precision Oncology
2025
•2025/12/31
0Accurate and efficient grade assessment of tumor budding (TB) in hematoxylin and eosin-stained whole slide images (H&E-stained WSIs) of colorectal cancer (CRC) remains challenging. This study proposes a full-automated TB annotation approach to assist in manual grade assessment by extracting tumo...
BiomarkersCancer
10.1038/S41698-025-01238-4
ISSN:2397-768X
LMNA-PRKDC axis enhances DNA repair and promotes chemoresistance in glioblastoma
Miranda R. Saathoff•Rafal Chojak•Rebecca X. Chen•Hasaan A. Kazi•Umme H. Faisal等 15 人
Cell Death & Disease
2025
•2025/11/21
0Glioblastoma (GBM) remains one of the deadliest primary brain tumors, with rapid recurrence and near-universal resistance to temozolomide (TMZ) limiting long-term survival. In this study, we identify a clinically actionable mechanism of resistance driven by the LMNA–PRKDC axis, which enhances DNA re...
Cell signallingCNS cancer
10.1038/S41419-025-08226-3
ISSN:2041-4889
MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial
Martin Wermke•Sebastian Ochsenreither•Dirk Jaeger•Heiko Becker•Annalen Bleckmann等 27 人
Nature Medicine
2026
•2026/5/31
•00 p.1-10
IMA401 is a T cell receptor (TCR)-based next-generation bispecific T cell engaging receptor (TCER) targeting an HLA-A*02:01-presented peptide derived from MAGE-A4/MAGE-A8 with its high-affinity TCR-based domain, incorporating a low-affinity T-cell-recruiting domain and an optimized Fc domain to prol...
Drug developmentMedical research
10.1038/S41591-026-04455-X
ISSN:1078-8956
Super-enhancer-associated long noncoding RNA lnc-SPI1U mediates SPI1 feedback regulation by interacting with HNRNPH1 and HNRNPF
Xuefei Ma•Yilu Li•Weifen Sun•Jiacheng Lou•Yi Zhang等 8 人
Oncogene
2025
•2025/10/24
•00 p.1-13
Long noncoding RNAs (lncRNAs) have been extensively studied for their regulatory roles in gene expression; however, relatively little is known about those specifically associated with super-enhancers (SEs)—genomic elements crucial for maintaining cell identity and function. This study profiles acute...
Acute myeloid leukaemiaNon-coding RNAs
10.1038/S41388-025-03612-9
ISSN:0950-9232
Categorical and phenotypic image synthetic learning as an alternative to federated learning
Nghi C. D. Truong•Chandan Ganesh Bangalore Yogananda•Benjamin C. Wagner•James M. Holcomb•Divya D. Reddy等 16 人
Nature Communications
2025
•2025/10/23
•Vol.16 No.1 p.1-11
Multi-center collaborations are crucial in developing robust and generalizable machine learning models in medical imaging. Traditional methods, such as centralized data sharing or federated learning (FL), face challenges, including privacy issues, communication burdens, and synchronization complexit...
Cancer imagingCNS cancerMachine learning
10.1038/S41467-025-64385-Z
ISSN:2041-1723
Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors
Marie-Paule Sablin•Pierre Gestraud•Sarah Flora Jonas•Constance Lamy•Magali Lacroix-Triki等 22 人
British Journal Of Cancer
2024
•2024/8/2
•00 p.1-8
Copy number alterations (CNA) are acquired during the evolution of cancers from their early stage to metastatic stage. This study aims at analysing the clinical value of the identified metastasis-associated CNAs both in metastatic breast cancers (mBCs) and early breast cancers (eBCs). Single-nucleot...
Breast cancerMetastasis
10.1038/S41416-024-02804-6
ISSN:0007-0920
Broad misappropriation of developmental splicing profile by cancer in multiple organs
Singh Arashdeep•Rajeevan Arati•Gopalan Vishaka•Agrawal Piyush•Day Chi-Ping等 6 人
Nature Communications
2022
•2022/12/12
•Vol.13 No.1 p.1-18
Oncogenesis mimics key aspects of embryonic development. However, the underlying mechanisms are incompletely understood. Here, we demonstrate that the splicing events specifically active during human organogenesis, are broadly reactivated in the organ-specific tumor. Such events are associated with ...
CancerDevelopmental biologyGene regulatory networksMembrane traffickingRNA
10.1038/S41467-022-35322-1
ISSN:2041-1723
IL-2 delivery by engineered mesenchymal stem cells re-invigorates CD8+ T cells to overcome immunotherapy resistance in cancer
Bae Joonbeom•Liu Longchao•Moore Casey•Hsu Eric•Zhang Anli等 12 人
Nature Cell Biology
2022
•2022/12/6
•Vol.24 No.12 p.1754-1765
Immune checkpoint blockade (ICB)-based immunotherapy depends on functional tumour-infiltrating lymphocytes (TILs), but essential cytokines are less understood. Here we uncover an essential role of endogenous IL-2 for ICB responsiveness and the correlation between insufficient IL-2 signalling and T-c...
Cancer immunotherapyImmunotherapy
10.1038/S41556-022-01024-5
ISSN:1465-7392
The liver microenvironment orchestrates FGL1-mediated immune escape and progression of metastatic colorectal cancer
Jia-Jun Li•Jin-Hong Wang•Tian Tian•Jia Liu•Yong-Qiang Zheng等 17 人
Nature Communications
2023
•2023/10/23
•Vol.14 No.1 p.1-18
Colorectal cancer (CRC) patients with liver metastases usually obtain less benefit from immunotherapy, and the underlying mechanisms remain understudied. Here, we identify that fibrinogen-like protein 1 (FGL1), secreted from cancer cells and hepatocytes, facilitates the progression of CRC in an intr...
Cancer immunotherapyColorectal cancerMetastasis
10.1038/S41467-023-42332-0
ISSN:2041-1723
Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing
Jian Liu•Chunxiao Li•Jinsong Wang•Dongkui Xu•Haijuan Wang等 18 人
Nature Communications
2020
•2020/9/8
•Vol.11 No.1 p.1-17
Dysregulated alternative splicing (AS) driving carcinogenetic mitosis remains poorly understood. Here, we demonstrate that cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, broadly interacts and co-expresses with RBPs across cancers, contributing to cancerous ...
Oncogenes
10.1038/S41467-020-18259-1
ISSN:2041-1723
Multimodal data integration using machine learning improves risk stratification of high-grade serous ovarian cancer
Boehm Kevin M.•Aherne Emily A.•Ellenson Lora•Nikolovski Ines•Alghamdi Mohammed等 27 人
Nature Cancer
2022
•2022/6/28
•Vol.3 No.6 p.723-733
Patients with high-grade serous ovarian cancer suffer poor prognosis and variable response to treatment. Known prognostic factors for this disease include homologous recombination deficiency status, age, pathological stage and residual disease status after debulking surgery. Recent work has highligh...
CancerData integrationMachine learningOvarian cancer
10.1038/S43018-022-00388-9
ISSN:2662-1347
PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma
Yao Xiaosai•Hong Jing Han•Nargund Amrita M.•Ng Michelle Shu Wen•Heng Hong Lee等 41 人
Nature Cell Biology
2023
•2023/4/24
•00 p.1-13
PBRM1 encodes an accessory subunit of the PBAF SWI/SNF chromatin remodeller, and the inactivation of PBRM1 is a frequent event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodelling is not well examined. Here we show that, in VHL-deficient renal tumours, PBRM1 deficiency result...
EpigenomicsRenal cancer
10.1038/S41556-023-01122-Y
ISSN:1465-7392
Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients
JungHo Kong•Heetak Lee•Donghyo Kim•Seong Kyu Han•Doyeon Ha等 7 人
Nature Communications
2020
•2020/10/30
•Vol.11 No.1 p.1-13
Cancer patient classification using predictive biomarkers for anti-cancer drug responses is essential for improving therapeutic outcomes. However, current machine-learning-based predictions of drug response often fail to identify robust translational biomarkers from preclinical models. Here, we pres...
Drug developmentGene regulatory networksMachine learning
10.1038/S41467-020-19313-8
ISSN:2041-1723
Ecologically sustainable benchmarking of AI models for histopathology
Yu-Chia Lan•Martin Strauch•Pourya Pilva•Nikolas E. J. Schmitz•Alireza Vafaei Sadr等 12 人
Npj Digital Medicine
2024
•2024/12/24
•Vol.7 No.1 p.1-11
Deep learning (DL) holds great promise to improve medical diagnostics, including pathology. Current DL research mainly focuses on performance. DL implementation potentially leads to environmental consequences but approaches for assessment of both performance and carbon footprint are missing. Here, w...
Computational scienceMedical research
10.1038/S41746-024-01397-X
ISSN:2398-6352
The novel endogenous micropeptide XLH-36 binds Gemin4 to promote triple-negative breast cancer metastasis
Mengwei Li•Wenwei Xie•Kexin Hu•Tiantian Li•Xin Li等 9 人
Oncogene
2025
•2025/11/29
•00 p.1-14
Triple-negative breast cancer (TNBC) is the most malignant breast cancer subtype. The 5-year overall survival rate of TNBC patients is 77%, but once cancer metastasis occurs, this rate drops to 12%. To date, the discovery of biomarkers associated with TNBC metastasis remains a major challenge. In th...
Breast cancerCell migration
10.1038/S41388-025-03621-8
ISSN:0950-9232
Image analysis reveals molecularly distinct patterns of TILs in NSCLC associated with treatment outcome
Ding Ruiwen•Prasanna Prateek•Corredor Germán•Barrera Cristian•Zens Philipp等 19 人
Npj Precision Oncology
2022
•2022/6/3
•Vol.6 No.1 p.1-15
Despite known histological, biological, and clinical differences between lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), relatively little is known about the spatial differences in their corresponding immune contextures. Our study of over 1000 LUAD and LUSC tumors revealed that comput...
CancerNon-small-cell lung cancer
10.1038/S41698-022-00277-5
ISSN:2397-768X
Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy
Álvarez-Varela Adrián•Novellasdemunt Laura•Barriga Francisco M.•Hernando-Momblona Xavier•Cañellas-Socias Adrià等 23 人
Nature Cancer
2022
•2022/6/30
•00 p.1-19
Colorectal cancer (CRC) patient-derived organoids predict responses to chemotherapy. Here we used them to investigate relapse after treatment. Patient-derived organoids expand from highly proliferative LGR5+ tumor cells; however, we discovered that lack of optimal growth conditions specifies a laten...
Cancer stem cellsCancer therapeutic resistanceChemotherapyColon cancer
10.1038/S43018-022-00402-0
ISSN:2662-1347
A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages
Thomas B. Huffaker•H. Atakan Ekiz•Cindy Barba•Soh-Hyun Lee•Marah C. Runtsch等 13 人
Nature Communications
2021
•2021/5/11
•Vol.12 No.1 p.1-19
Tumor associated macrophage responses are regulated by distinct metabolic states that affect their function. However, the ability of specific signals in the local tumor microenvironment to program macrophage metabolism remains under investigation. Here, we identify NAMPT, the rate limiting enzyme in...
Gene regulation in immune cellsImmunologyInnate immunityTumour immunology
10.1038/S41467-021-22923-5
ISSN:2041-1723
A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma
Akimasa Hayashi•Jun Fan•Ruoyao Chen•Yu-jui Ho•Alvin P. Makohon-Moore等 29 人
Nature Cancer
2020
•2020/1/13
•Vol.1 No.1 p.59-74
Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion-sampled metastatic pancreatic cancers, finding that squamous fea...
Cancer genomicsPancreatic cancerTumour heterogeneity
10.1038/S43018-019-0010-1
ISSN:2662-1347
2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer
Arnaud Blomme•Catriona A. Ford•Ernest Mui•Rachana Patel•Chara Ntala等 25 人
Nature Communications
2020
•2020/5/19
•Vol.11 No.1 p.1-17
Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation of LNCaP cells chronically exposed to multi...
Cancer metabolismLipidomicsMetabolomicsProstate cancerProteomics
10.1038/S41467-020-16126-7
ISSN:2041-1723
Essential genes shape cancer genomes through linear limitation of homozygous deletions
Maroulio Pertesi•Ludvig Ekdahl•Angelica Palm•Ellinor Johnsson•Linnea Järvstråt等 7 人
Communications Biology
2019
•2019/7/19
•Vol.2 No.1 p.1-11
The landscape of somatic acquired deletions in cancer cells is shaped by positive and negative selection. Recurrent deletions typically target tumor suppressor, leading to positive selection. Simultaneously, loss of a nearby essential gene can lead to negative selection, and introduce latent vulnera...
Cancer genomicsComputational modelsLung cancer
10.1038/S42003-019-0517-0
ISSN:2399-3642
Pan-cancer transcriptomic analysis identified six classes of immunosenescence genes revealed molecular links between aging, immune system and cancer
Wang Xinyue•Guo Shuang•Zhou Hanxiao•Sun Yue•Gan Jing等 13 人
Genes & Immunity
2023
•2023/2/17
•00 p.1-11
Aging is a complex process that significantly impacts the immune system. The aging-related decline of the immune system, termed immunosenescence, can lead to disease development, including cancer. The perturbation of immunosenescence genes may characterize the associations between cancer and aging. ...
Gene expressionImmunotherapy
10.1038/S41435-023-00197-9
ISSN:1476-5470
Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia
Cindrilla Chumduri•Rajendra Kumar Gurumurthy•Hilmar Berger•Oliver Dietrich•Naveen Kumar等 18 人
Nature Cell Biology
2021
•2021/1/18
•Vol.23 No.2 p.184-197
The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche i...
CancerCell signallingDevelopmental biologyStem cells
10.1038/S41556-020-00619-0
ISSN:1465-7392
The ETS transcription factor GABPA inhibits bladder cancer aggressiveness by repressing extracellular matrix deposition and mechanotransduction signaling
Mingkai Dai•Xiaotian Yuan•Chenxi Sun•Runyuan Han•Magnus Björkholm等 8 人
Cell Death & Disease
2025
•2025/8/14
•Vol.16 No.1 p.1-14
The ETS transcription factor GABPA exhibits an oncogenic effect by activating telomerase in many cancers; however, some studies imply its tumor suppressive activities. It is thus important to define its different roles in oncogenesis. By examining GABPA-transgenic mice, we unexpectedly observed that...
Cancer microenvironmentOncogenesis
10.1038/S41419-025-07935-Z
ISSN:2041-4889
Multimodal fusion of pathology and radiology foundation models for WHO 2021 glioma subtyping
Camillo Saueressig•Daniel Scholz•Philipp Raffler•Claire Delbridge•Benedikt Wiestler等 6 人
Npj Precision Oncology
2026
•2026/3/12
•Vol.10 No.1 p.1180
Molecular subtyping of gliomas is a common clinical task, yet challenging to perform on histology or radiology images alone. To address this challenge, we developed a multimodal classification framework that integrates histopathology and magnetic resonance imaging (MRI) using foundation models as un...
BiomarkersCancerComputational biology and bioinformaticsMedical researchOncology
10.1038/S41698-026-01366-5
ISSN:2397-768X
Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT
Kang Xing•Xu En•Wang Xingzhou•Qian Lulu•Yang Zhi等 13 人
Cell Death & Disease
2021
•2021/9/29
•Vol.12 No.10 p.1-11
Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of ...
Gastric cancerTumour angiogenesis
10.1038/S41419-021-04153-1
ISSN:2041-4889
The Molecular Twin artificial-intelligence platform integrates multi-omic data to predict outcomes for pancreatic adenocarcinoma patients
Arsen Osipov•Ognjen Nikolic•Arkadiusz Gertych•Sarah Parker•Andrew Hendifar等 14 人
Nature Cancer
2024
•2024/1/22
•00 p.1-16
Contemporary analyses focused on a limited number of clinical and molecular biomarkers have been unable to accurately predict clinical outcomes in pancreatic ductal adenocarcinoma. Here we describe a precision medicine platform known as the Molecular Twin consisting of advanced machine-learning mode...
Machine learningPancreatic cancerPredictive markersPrognostic markers
10.1038/S43018-023-00697-7
ISSN:2662-1347
AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress
Xuewei Zhai•Ronghui Yang•Qiaoyun Chu•Zihao Guo•Pengjiao Hou等 12 人
Nature Cell Biology
2025
•2025/1/2
•00 p.1-13
Glucose metabolism has been studied extensively, but the role of glucose-derived excretory glycerol remains unclear. Here we show that hypoxia induces NADH accumulation to promote glycerol excretion and this pathway consumes NADH continuously, thus attenuating its accumulation and reductive stress. ...
Cancer metabolismCell growthStress signalling
10.1038/S41556-024-01549-X
ISSN:1465-7392
A complex epigenome-splicing crosstalk governs epithelial-to-mesenchymal transition in metastasis and brain development
Sahu Sanjeeb Kumar•Agirre Eneritz•Inayatullah Mohammed•Mahesh Arun•Tiwari Neha等 12 人
Nature Cell Biology
2022
•2022/8/8
•Vol.24 No.8 p.1265-1277
Epithelial-to-mesenchymal transition (EMT) renders epithelial cells migratory properties. While epigenetic and splicing changes have been implicated in EMT, the mechanisms governing their crosstalk remain poorly understood. Here we discovered that a C2H2 zinc finger protein, ZNF827, is strongly indu...
EpigeneticsEpithelial–mesenchymal transitionMetastasisRNA splicing
10.1038/S41556-022-00971-3
ISSN:1465-7392
SPRTN is involved in hepatocellular carcinoma development through the ER stress response
Anja Batel•Mirjana Polović•Mateo Glumac•Oliver Šuman•Stipislav Jadrijević等 13 人
Cancer Gene Therapy
2023
•2023/12/12
•00 p.1-11
Endoplasmic reticulum (ER) stress, prompted by the accumulation of misfolded or unfolded proteins, triggers the activation of the unfolded protein response (UPR) pathway to restore ER homeostasis. This stress response is implicated in the development of hepatocellular carcinoma (HCC). A biallelic mu...
Cell biologyLiver cancerMolecular biology
10.1038/S41417-023-00708-W
ISSN:0929-1903
Radiation-induced amphiregulin drives tumour metastasis
András Piffkó•Kaiting Yang•Arpit Panda•Janna Heide•Krystyna Tesak等 23 人
Nature
2025
•2025/5/14
•00 p.1-10
The anti-tumour effect of radiotherapy beyond the treatment field—the abscopal effect—has garnered much interest1. However, the potentially deleterious effect of radiation in promoting metastasis is less well studied. Here we show that radiotherapy induces the expression of the EGFR ligand amphiregu...
MetastasisRadiotherapy
10.1038/S41586-025-08994-0
ISSN:0028-0836
Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry
Amit Kulkarni•Tiago Ferreira•Clemens Bretscher•Annabel Grewenig•Nazim El-Andaloussi等 19 人
Nature Communications
2021
•2021/6/22
•Vol.12 No.1 p.1-18
H-1 parvovirus (H-1PV) is a promising anticancer therapy. However, in-depth understanding of its life cycle, including the host cell factors needed for infectivity and oncolysis, is lacking. This understanding may guide the rational design of combination strategies, aid development of more effective...
Cancer immunotherapyVirus–host interactions
10.1038/S41467-021-24034-7
ISSN:2041-1723
The landscape of B and plasma cells in breast cancer: insights from single-cell and spatial transcriptomics
Xing Cai•Jinru Yang•Wenzheng Wang•Xiaolu Zhan•Xiaohan Chen等 13 人
Npj Breast Cancer
2026
•2026/3/12
0Tumor-associated B (TAB) cells and plasma cells are increasingly recognized as key components of the tumor microenvironment; however, their heterogeneity and functional roles in breast cancer remain incompletely understood. Here, by integrating publicly available single-cell RNA (scRNA) sequencing d...
BiomarkersCancerGenetics
10.1038/S41523-026-00917-0
ISSN:2374-4677
Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers
Sherille D. Bradley•Amjad H. Talukder•Ivy Lai•Rebecca Davis•Hector Alvarez等 32 人
Nature Communications
2020
•2020/10/21
•Vol.11 No.1 p.1-12
Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regressions by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bou...
BiotechnologyCancerCancer immunotherapyImmunologyTargeted therapies
10.1038/S41467-020-19141-W
ISSN:2041-1723
IL-27 elicits a cytotoxic CD8+ T cell program to enforce tumour control
Béatrice Bréart•Katherine Williams•Stellanie Krimm•Tiffany Wong•Brandon D. Kayser等 37 人
Nature
2025
•2025/2/5
•Vol.639 No.8055 p.746-753
Although cytotoxic CD8+ T lymphocytes (CTLs) are essential for anti-tumour immunity, they are frequently dysfunctional in tumours1. Cytokines that sustain CTL activity are attractive for cancer immunotherapy, but avoiding inflammatory toxicity remains a challenge for their clinical use2. Here we sho...
Cytotoxic T cellsInterleukinsTumour immunology
10.1038/S41586-024-08510-W
ISSN:0028-0836
ECM-based molecular subtypes define prognostic, EMT status, and therapeutic diversity in IDH-mutant gliomas
Yanfei Wei•Di Chen•Qian Zhang•Fenfen You•YiLong Fu等 11 人
Npj Precision Oncology
2025
•2025/8/27
•Vol.9 No.1 p.1-16
IDH-mutant gliomas show prognostic heterogeneity despite favorable overall outcomes, necessitating refined molecular classification. While the extracellular matrix (ECM) critically regulates tumor progression, immunity, and EMT, its prognostic significance in IDH-mutant gliomas remains largely unexp...
CancerCNS cancerImmunology
10.1038/S41698-025-01100-7
ISSN:2397-768X
TRIP13, identified as a hub gene of tumor progression, is the target of microRNA-4693-5p and a potential therapeutic target for colorectal cancer
Chen Yan•Chen Danqi•Qin Ying•Qiu Cheng•Zhou Yaoyao等 9 人
Cell Death Discovery
2022
•2022/1/24
•Vol.8 No.1 p.1-10
Colorectal cancer (CRC) is one of the digestive tract malignancies whose early symptoms are not obvious. This study aimed to identify novel targets for CRC therapy, especially early-stage CRC, by reanalyzing the publicly available GEO and TCGA databases. Thyroid hormone receptor interactor 13 (TRIP1...
OncogenesTumour biomarkers
10.1038/S41420-022-00824-W
ISSN:2058-7716
Phase separation of phospho-HDAC6 drives aberrant chromatin architecture in triple-negative breast cancer
Bing Lu•Ru Qiu•Jiatian Wei•Li Wang•Qinkai Zhang等 17 人
Nature Cancer
2024
•2024/8/28
•00 p.1-19
How dysregulated liquid–liquid phase separation (LLPS) contributes to the oncogenesis of female triple-negative breast cancer (TNBC) remains unknown. Here we demonstrate that phosphorylated histone deacetylase 6 (phospho-HDAC6) forms LLPS condensates in the nuclei of TNBC cells that are essential fo...
CancerCancer therapyCell biology
10.1038/S43018-024-00816-Y
ISSN:2662-1347
ISGylation prevents autophagic degradation of STING and promotes antitumor immunity in lung cancer
Dan Cao•Bin Huang•Xinming Fu•Ming Liu•Xiaogang Niu等 7 人
Cell Death & Disease
2026
•2026/2/27
•Vol.17 No.1 p.2710
The STING pathway plays a central role in immune activation; however, STING protein levels decline during the progression of various cancers, including lung cancer, thereby limiting the efficacy of immunotherapies. Our study uncovers a previously unrecognized mechanism whereby ISGylation stabilizes ...
Post-translational modificationsSignal transduction
10.1038/S41419-026-08527-1
ISSN:2041-4889
Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy
Riyao Yang•Linlin Sun•Ching-Fei Li•Yu-Han Wang•Jun Yao等 17 人
Nature Communications
2021
•2021/2/5
•Vol.12 No.1 p.1-17
The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to th...
CancerCancer immunotherapyCell biologyImmunologyTumour immunology
10.1038/S41467-021-21099-2
ISSN:2041-1723
Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma
Katey S. S. Enfield•Erin A. Marshall•Christine Anderson•Kevin W. Ng•Sara Rahmati等 21 人
Nature Communications
2019
•2019/11/28
•Vol.10 No.1 p.1-13
Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUA...
CancerCancer geneticsCancer genomicsCancer modelsLung cancer
10.1038/S41467-019-13295-Y
ISSN:2041-1723
Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes
Lee Hyo-Jung•Song Kwon-Ho•Oh Se Jin•Kim Suyeon•Cho Eunho等 14 人
Nature Communications
2022
•2022/4/19
•Vol.13 No.1 p.1-17
Immunotherapy has emerged as a powerful approach to cancer treatment. However, immunotherapeutic resistance limits its clinical application. Therefore, identifying immune-resistant factors, which can be targeted by clinically available drugs and it also can be a companion diagnostic marker, is neede...
Cancer immunotherapyImmunoediting
10.1038/S41467-022-29611-Y
ISSN:2041-1723
SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers
Shi Lei•Shen William•Davis Mindy I.•Kong Ke•Vu Phuong等 39 人
Nature Cancer
2023
•2023/3/13
•Vol.4 No.3 p.365-381
Adult liver malignancies, including intrahepatic cholangiocarcinoma and hepatocellular carcinoma, are the second leading cause of cancer-related deaths worldwide. Most individuals are treated with either combination chemotherapy or immunotherapy, respectively, without specific biomarkers for selecti...
CancerCancer therapyDrug developmentMechanism of action
10.1038/S43018-023-00523-0
ISSN:2662-1347
Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer
Stackpole Mary L.•Zeng Weihua•Li Shuo•Liu Chun-Chi•Zhou Yonggang等 40 人
Nature Communications
2022
•2022/9/29
•Vol.13 No.1 p.1-12
Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It con...
Cancer screeningComputational biology and bioinformaticsDiagnostic markersSoftwareStatistical methods
10.1038/S41467-022-32995-6
ISSN:2041-1723
wMKL: multi-omics data integration enables novel cancer subtype identification via weight-boosted multi-kernel learning
Hongyan Cao•Congcong Jia•Zhi Li•Haitao Yang•Ruiling Fang等 7 人
British Journal Of Cancer
2024
•2024/1/26
•00 p.1-12
Cancer is a heterogeneous disease driven by complex molecular alterations. Cancer subtypes determined from multi-omics data can provide novel insight into personalised precision treatment. It is recognised that incorporating prior weight knowledge into multi-omics data integration can improve diseas...
Data integrationStatistical methods
10.1038/S41416-024-02587-W
ISSN:0007-0920
Data-driven energy landscape reveals critical genes in cancer progression
Juntan Liu•Chunhe Li
Npj Systems Biology And Applications
2024
•2024/3/8
•Vol.10 No.1 p.1-11
The evolution of cancer is a complex process characterized by stable states and transitions among them. Studying the dynamic evolution of cancer and revealing the mechanisms of cancer progression based on experimental data is an important topic. In this study, we aim to employ a data-driven energy l...
CancerMultistability
10.1038/S41540-024-00354-4
ISSN:2056-7189
FGFR1 suppresses ovarian cancer progression by modulating SIRT3-dependent lactylation and metabolic reprogramming
Fan Jiang•Huaju Huang•Zhe Dong•Lu Zhang•Shiti Zhang等 9 人
Cell Death Discovery
2026
•2026/4/7
0Ovarian cancer (OC) is an aggressive gynecological malignancy with poor prognosis, largely due to late-stage diagnosis and high metastatic potential. However, the functional role and regulatory mechanisms of fibroblast growth factor receptor 1 (FGFR1) in OC remain incompletely understood. In this st...
Cancer metabolismPrognostic markers
10.1038/S41420-026-03054-6
ISSN:2058-7716
Inhibiting macrophage-derived lactate transport restores cGAS–STING signalling and enhances antitumour immunity in glioblastoma
Daqi Li•Gaoyuan Cui•Kailin Yang•Chenfei Lu•Yuhan Jiang等 30 人
Nature Cell Biology
2026
•2026/1/6
•Vol.28 No.2 p.349-362
Glioblastoma (GBM) is a malignancy with a complex tumour microenvironment (TME) dominated by GBM stem cells (GSCs) and infiltrated by tumour-associated macrophages (TAMs) and exhibits aberrant metabolic pathways. Lactate is a critical glycolytic metabolite that promotes tumour progression; however, ...
Cancer stem cellsCNS cancerPost-translational modificationsTumour immunology
10.1038/S41556-025-01839-Y
ISSN:1465-7392
Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma
Dimitra Kerdidani•Panagiotis Chouvardas•Ares Rocanin Arjo•Ioanna Giopanou•Giannoula Ntaliarda等 15 人
Nature Communications
2019
•2019/3/29
•Vol.10 No.1 p.1-16
Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic gen...
Cancer immunotherapyNon-small-cell lung cancerTumour immunology
10.1038/S41467-019-09370-Z
ISSN:2041-1723
Acute lymphoblastic leukemia displays a distinct highly methylated genome
Hetzel Sara•Mattei Alexandra L.•Kretzmer Helene•Qu Chunxu•Chen Xiang等 18 人
Nature Cancer
2022
•2022/5/19
•00 p.1-15
DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood ca...
CancerCancer epigeneticsCancer genomicsHaematological cancer
10.1038/S43018-022-00370-5
ISSN:2662-1347
Pan-cancer landscape of epigenetic factor expression predicts tumor outcome
Michael W. Cheng•Mithun Mitra•Hilary A. Coller
Communications Biology
2023
•2023/11/16
•Vol.6 No.1 p.1-18
Oncogenic pathways that drive cancer progression reflect both genetic changes and epigenetic regulation. Here we stratified primary tumors from each of 24 TCGA adult cancer types based on the gene expression patterns of epigenetic factors (epifactors). The tumors for five cancer types (ACC, KIRC, LG...
Cancer genomicsMachine learning
10.1038/S42003-023-05459-W
ISSN:2399-3642
Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer
Hammerl Dora•Martens John W. M.•Timmermans Mieke•Smid Marcel•Trapman-Jansen Anita M.等 15 人
Nature Communications
2021
•2021/9/27
•Vol.12 No.1 p.1-13
Only a subgroup of triple-negative breast cancer (TNBC) responds to immune checkpoint inhibitors (ICI). To better understand lack of response to ICI, we analyze 681 TNBCs for spatial immune cell contextures in relation to clinical outcomes and pathways of T cell evasion. Excluded, ignored and inflam...
BiomarkersCancerDiseasesImmunologyMedical research
10.1038/S41467-021-25962-0
ISSN:2041-1723
Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial
Martin Wermke•Dejka M. Araurjo•Manik Chatterjee•Apostolia M. Tsimberidou•Tobias A. W. Holderried等 40 人
Nature Medicine
2025
•2025/4/9
•00 p.1-10
In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, mu...
Cancer immunotherapyHead and neck cancerMelanomaSarcoma
10.1038/S41591-025-03650-6
ISSN:1078-8956
MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data
Theodore Sakellaropoulos•Catherine Do•Guimei Jiang•Giulia Cova•Peter Meyn等 10 人
Nature Communications
2024
•2024/7/17
•Vol.15 No.1 p.1-15
Aberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we ...
Cancer epigeneticsCancer genomicsGene regulatory networksSoftware
10.1038/S41467-024-50380-3
ISSN:2041-1723
Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity
Andreas Heindl•Adnan Mujahid Khan•Daniel Nava Rodrigues•Katherine Eason•Anguraj Sadanandam等 11 人
Nature Communications
2018
•2018/9/25
•Vol.9 No.1 p.1-14
How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to define cancer morphological diversification within the spatial context of the m...
EcologyOvarian cancer
10.1038/S41467-018-06130-3
ISSN:2041-1723
Glioblastoma glycolytic signature predicts unfavorable prognosis, immunological heterogeneity, and ENO1 promotes microglia M2 polarization and cancer cell malignancy
Liang Xisong•Wang Zeyu•Dai Ziyu•Zhang Hao•Zhang Jian等 11 人
Cancer Gene Therapy
2022
•2022/12/9
•Vol.30 No.3 p.481-496
Glioblastomas are the most malignant brain tumors, whose progress was promoted by aberrate aerobic glycolysis. The immune environment was highly engaged in glioblastoma formation, while its interaction with aerobic glycolysis remained unclear. Herein, we build a 7-gene Glycolytic Score (GS) by Elast...
BiomarkersCancer microenvironmentCNS cancerTumour immunology
10.1038/S41417-022-00569-9
ISSN:0929-1903
U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies
Molly A. Smith•Gaurav S. Choudhary•Andrea Pellagatti•Kwangmin Choi•Lyndsey C. Bolanos等 20 人
Nature Cell Biology
2019
•2019/4/22
•Vol.21 No.5 p.640-650
Spliceosome mutations are common in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), but the oncogenic changes due to these mutations have not been identified. Here a global analysis of exon usage in AML samples revealed distinct molecular subsets containing alternative spliced iso...
CancerNF-kappaBOncogenesRNA splicing
10.1038/S41556-019-0314-5
ISSN:1465-7392
Low-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8+ exhausted-like T cells
Siqi Li•Kun Li•Kang Wang•Haoyuan Yu•Xiangyang Wang等 15 人
Nature Communications
2023
•2023/11/24
•Vol.14 No.1 p.1-21
Atezolizumab (anti-PD-L1) combined with bevacizumab (anti-VEGFA) is the first-line immunotherapy for advanced hepatocellular carcinoma (HCC), but the number of patients who benefit from this regimen remains limited. Here, we combine dual PD-L1 and VEGFA blockade (DPVB) with low-dose radiotherapy (LD...
Cancer therapyHepatocellular carcinomaRadiotherapyTumour immunology
10.1038/S41467-023-43462-1
ISSN:2041-1723
RFC4 drives temozolomide resistance in glioblastoma by activating STK38-BECN1-dependent autophagy
Min Mao•Hang Ji•Wen-Qian Yu•Qu-Jing Gai•Qiang Sun等 14 人
Nature Communications
2026
•2026/3/23
0Glioblastoma (GBM) remains a lethal brain tumor due to therapy resistance. While autophagy contributes to temozolomide (TMZ) resistance, its regulation is incompletely understood. This study investigates the role of replication factor RFC4, which is associated with poor prognosis and TMZ resistance ...
CancerCancer therapeutic resistanceCNS cancer
10.1038/S41467-026-70798-1
ISSN:2041-1723
Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity
Joanna R. Kovalski•Goksu Sarioglu•Vishvak Subramanyam•Grace Hernandez•Gilles Rademaker等 17 人
Nature Cell Biology
2025
•2025/2/4
•Vol.27 No.3 p.518-529
Oncogenic protein dosage is tightly regulated to enable cancer formation but how this is regulated by translational control remains unknown. The Myc oncogene is a paradigm of an exquisitely regulated oncogene and a driver of pancreatic ductal adenocarcinoma (PDAC). Here we use a CRISPR interference ...
OncogenesPancreatic cancerTranslation
10.1038/S41556-024-01604-7
ISSN:1465-7392
Dual-inhibition of NAMPT and PAK4 induces anti-tumor effects in 3D-spheroids model of platinum-resistant ovarian cancer
Kei Kudo•Yoshimi Endo Greer•Teruhiko Yoshida•Brittney S. Harrington•Soumya Korrapati等 11 人
Cancer Gene Therapy
2024
•2024/2/29
•00 p.1-15
Ovarian cancer follows a characteristic progression pattern, forming multiple tumor masses enriched with cancer stem cells (CSCs) within the abdomen. Most patients develop resistance to standard platinum-based drugs, necessitating better treatment approaches. Targeting CSCs by inhibiting NAD+ synthe...
Cancer stem cellsCell biologyOvarian cancer
10.1038/S41417-024-00748-W
ISSN:0929-1903
The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses chromosome translocation during tumorigenesis
Wen Li•Xiuzhen Bai•Jun Li•Yichao Zhao•Jingyan Liu等 17 人
Nature Cell Biology
2019
•2019/9/23
•Vol.21 No.10 p.1273-1285
Chromosome translocation is a major cause of the onset and progression of diverse types of cancers. However, the mechanisms underlying this process remain poorly understood. Here, we identified a non-homologous end-joining protein, IFFO1, which structurally forms a heterotetramer with XRCC4. IFFO1 i...
CancerCytoskeletonNon-homologous-end joining
10.1038/S41556-019-0388-0
ISSN:1465-7392
Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming
Xujia Wu•Huairui Yuan•Qiulian Wu•Yixin Gao•Tingting Duan等 20 人
Nature Cancer
2024
•2024/3/22
•00 p.1-21
Cancers commonly reprogram translation and metabolism, but little is known about how these two features coordinate in cancer stem cells. Here we show that glioblastoma stem cells (GSCs) display elevated protein translation. To dissect underlying mechanisms, we performed a CRISPR screen and identifie...
CancerCancer stem cellsCancer therapyCNS cancer
10.1038/S43018-024-00748-7
ISSN:2662-1347
UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination
Jiang Liu•Di Guan•Maogong Dong•Jingjing Yang•Haibin Wei等 16 人
Nature Cell Biology
2020
•2020/8/17
•Vol.22 No.9 p.1056-1063
p53 is the most intensively studied tumour suppressor1. The regulation of p53 homeostasis is essential for its tumour-suppressive function2,3. Although p53 is regulated by an array of post-translational modifications, both during normal homeostasis and in stress-induced responses2–4, how p53 maintai...
CancerDNA damage and repairTumour-suppressor proteinsUbiquitylation
10.1038/S41556-020-0559-Z
ISSN:1465-7392
Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity
Mengrui Liu•Shiqi Hu•Na Yan•Kristen D. Popowski•Ke Cheng
Nature Nanotechnology
2024
•2024/1/11
•00 p.1-11
Lung carcinoma is one of the most common cancers and has one of the lowest survival rates in the world. Cytokines such as interleukin-12 (IL-12) have demonstrated considerable potential as robust tumour suppressors. However, their applications are limited due to off-target toxicity. Here we report o...
Drug deliveryNanoparticles
10.1038/S41565-023-01580-3
ISSN:1748-3387
Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signalling
Xinya Gao•Xin Xia•Fanying Li•Maolei Zhang•Huangkai Zhou等 16 人
Nature Cell Biology
2021
•2021/3/4
•Vol.23 No.3 p.278-291
Activated EGFR signalling drives tumorigenicity in 50% of glioblastoma (GBM). However, EGFR-targeting therapy has proven ineffective in treating patients with GBM, indicating that there is redundant EGFR activation. Circular RNAs are covalently closed RNA transcripts that are involved in various phy...
Cancer stem cellsCancer therapyCNS cancerGrowth factor signalling
10.1038/S41556-021-00639-4
ISSN:1465-7392
Extracellular cGAMP is a cancer-cell-produced immunotransmitter involved in radiation-induced anticancer immunity
Jacqueline A. Carozza•Volker Böhnert•Khanh C. Nguyen•Gemini Skariah•Kelsey E. Shaw等 12 人
Nature Cancer
2020
•2020/2/24
•Vol.1 No.2 p.184-196
2′3′-Cyclic GMP-AMP (cGAMP) is an intracellular second messenger that is synthesized in response to cytosolic double-stranded DNA and activates the innate immune STING pathway. Our previous discovery of its extracellular hydrolase ENPP1 hinted at the existence of extracellular cGAMP. Here we detecte...
BiochemistryTumour immunology
10.1038/S43018-020-0028-4
ISSN:2662-1347
C-IGF1R encoded by cIGF1R acts as a molecular switch to restrict mitophagy of drug-tolerant persister tumour cells in non-small cell lung cancer
Hui Wang•Yingkuan Liang•Te Zhang•Xinnian Yu•Xuming Song等 12 人
Cell Death & Differentiation
2023
•2023/9/9
•00 p.1-17
The clinical efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) is limited by the emergence of drug resistance. We hypothesise that restoring dysregulated circular RNAs under initial treatment with EGFR-TKIs may enhance their effectiveness. Through high-throughput sc...
Non-small-cell lung cancerTranslational research
10.1038/S41418-023-01222-0
ISSN:1350-9047
FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome
Fuming Li•Peiwei Huangyang•Michelle Burrows•Kathy Guo•Romain Riscal等 13 人
Nature Cell Biology
2020
•2020/5/4
•Vol.22 No.6 p.728-739
The crosstalk between deregulated hepatocyte metabolism and cells within the tumour microenvironment, as well as the consequent effects on liver tumorigenesis, are not completely understood. We show here that hepatocyte-specific loss of the gluconeogenic enzyme fructose 1,6-bisphosphatase 1 (FBP1) d...
Cancer metabolismCancer microenvironmentLiver cancerSenescence
10.1038/S41556-020-0511-2
ISSN:1465-7392
CAR-engineered lymphocyte persistence is governed by a FAS ligand–FAS autoregulatory circuit
Fei Yi•Tal Cohen•Natalie Zimmerman•Friederike Dündar•Paul Zumbo等 23 人
Nature Cancer
2025
•2025/7/22
•00 p.1-18
Chimeric antigen receptor (CAR)-engineered lymphocytes treat B cell malignancies; however, limited persistence can restrain the full therapeutic potential of this approach. FAS ligand (FAS-L)/FAS interactions govern lymphocyte homeostasis. Knowledge of which cells express FAS-L in patients with canc...
CancerTumour immunology
10.1038/S43018-025-01009-X
ISSN:2662-1347
EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation
Guo Gao•Gong Ke•Beckley Nicole•Zhang Yue•Yang Xiaoyao等 30 人
Nature Cell Biology
2022
•2022/8/1
•Vol.24 No.8 p.1291-1305
The epidermal growth factor receptor (EGFR) is a prime oncogene that is frequently amplified in glioblastomas. Here we demonstrate a new tumour-suppressive function of EGFR in EGFR-amplified glioblastomas regulated by EGFR ligands. Constitutive EGFR signalling promotes invasion via activation of a T...
Cell invasionCNS cancerGrowth factor signallingRHO signalling
10.1038/S41556-022-00962-4
ISSN:1465-7392
Reference-free deconvolution, visualization and interpretation of complex DNA methylation data using DecompPipeline, MeDeCom and FactorViz
Michael Scherer•Petr V. Nazarov•Reka Toth•Shashwat Sahay•Tony Kaoma等 11 人
Nature Protocols
2020
•2020/9/25
•Vol.15 No.10 p.3240-3263
DNA methylation profiling offers unique insights into human development and diseases. Often the analysis of complex tissues and cell mixtures is the only feasible option to study methylation changes across large patient cohorts. Since DNA methylomes are highly cell type specific, deconvolution metho...
CancerData integrationData processingDNA methylationStatistical methods
10.1038/S41596-020-0369-6
ISSN:1754-2189
Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma
Malgorzata Czystowska-Kuzmicz•Anna Sosnowska•Dominika Nowis•Kavita Ramji•Marta Szajnik等 23 人
Nature Communications
2019
•2019/7/5
•Vol.10 No.1 p.1-16
Tumor-driven immune suppression is a major barrier to successful immunotherapy in ovarian carcinomas (OvCa). Among various mechanisms responsible for immune suppression, arginase-1 (ARG1)-carrying small extracellular vesicles (EVs) emerge as important contributors to tumor growth and tumor escape fr...
Ovarian cancerTumour immunology
10.1038/S41467-019-10979-3
ISSN:2041-1723
Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes
Lulu Sun•Yuqing Wang•Jin Cen•Xiaolong Ma•Lei Cui等 20 人
Nature Cell Biology
2019
•2019/7/22
•Vol.21 No.8 p.1015-1026
Human liver cancers, including hepatocellular carcinomas and intra-hepatic cholangiocarcinomas, are often diagnosed late with poor prognosis. A better understanding of cancer initiation could provide potential preventive therapies and increase survival. Models for studying human liver cancer initiat...
CancerCancer modelsReprogramming
10.1038/S41556-019-0359-5
ISSN:1465-7392
Human T cells engineered with a leukemia lipid-specific TCR enables donor-unrestricted recognition of CD1c-expressing leukemia
Consonni Michela•Garavaglia Claudio•Grilli Andrea•de Lalla Claudia•Mancino Alessandra等 18 人
Nature Communications
2021
•2021/8/11
•Vol.12 No.1 p.1-14
Acute leukemia relapsing after chemotherapy plus allogeneic hematopoietic stem cell transplantation can be treated with donor-derived T cells, but this is hampered by the need for donor/recipient MHC-matching and often results in graft-versus-host disease, prompting the search for new donor-unrestri...
Acute myeloid leukaemiaAntigen presentationCancer immunotherapyCellular immunityLymphocyte activation
10.1038/S41467-021-25223-0
ISSN:2041-1723
Peripheral blood DNA methylation profiles predict future development of B-cell Non-Hodgkin Lymphoma
Espín-Pérez Almudena•Brennan Kevin•Ediriwickrema Asiri Saumya•Gevaert Olivier•Lossos Izidore S.等 6 人
Npj Precision Oncology
2022
•2022/7/21
•Vol.6 No.1 p.1-9
Lack of accurate methods for early lymphoma detection limits the ability to cure patients. Since patients with Non-Hodgkin lymphomas (NHL) who present with advanced disease have worse outcomes, accurate and sensitive methods for early detection are needed to improve patient care. We developed a DNA ...
B-cell lymphomaCancer genomicsHigh-throughput screening
10.1038/S41698-022-00295-3
ISSN:2397-768X
Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade
Vathiotis Ioannis A.•Salichos Leonidas•Martinez-Morilla Sandra•Gavrielatou Niki•Aung Thazin Nwe等 13 人
Npj Precision Oncology
2022
•2022/12/15
•Vol.6 No.1 p.1-8
Treatment with immune checkpoint inhibitors has altered the course of malignant melanoma, with approximately half of the patients with advanced disease surviving for more than 5 years after diagnosis. Currently, there are no biomarker methods for predicting outcome from immunotherapy. Here, we obtai...
MelanomaPredictive markers
10.1038/S41698-022-00330-3
ISSN:2397-768X
Ubenimex synergizes with the PD-L1 blockade in gastric cancer by competitively binding LAP3 with UBE3A
Caixia Zhao•Jiaxin Li•Jinxiu Zheng•Ming Chi•Ying Shao等 15 人
Cell Death & Disease
2026
•2026/2/26
•Vol.17 No.1 p.2410
Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 blockade, represent a cornerstone of treatment for advanced gastric cancer (GC). However, their clinical efficacy is hampered by low response rates and the development of both primary and acquired resistance, underscoring the need for inno...
Cancer immunotherapyCancer microenvironment
10.1038/S41419-026-08509-3
ISSN:2041-4889
TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
Bi Jing•Wu Zhihui•Zhang Xin•Zeng Taoling•Dai Wanjun等 24 人
Nature Communications
2023
•2023/4/24
•Vol.14 No.1 p.1-15
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR us...
Breast cancerCell signalling
10.1038/S41467-023-38115-2
ISSN:2041-1723
Intelligent feature engineering and ontological mapping of brain tumour histomorphologies by deep learning
Kevin Faust•Sudarshan Bala•Randy van Ommeren•Alessia Portante•Raniah Al Qawahmed等 7 人
Nature Machine Intelligence
2019
•2019/7/9
•Vol.1 No.7 p.316-321
Deep learning is an emerging transformative tool in diagnostic medicine, yet limited access and the interpretability of learned parameters hinders widespread adoption. Here we have generated a diverse repository of 838,644 histopathologic images and used them to optimize and discretize learned repre...
DiagnosisNervous system
10.1038/S42256-019-0068-6
ISSN:2522-5839
Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy
Yang Gao•Naoe Taira Nihira•Xia Bu•Chen Chu•Jinfang Zhang等 27 人
Nature Cell Biology
2020
•2020/8/24
•Vol.22 No.9 p.1064-1075
Immunotherapies that target programmed cell death protein 1 (PD-1) and its ligand PD-L1 as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) have shown impressive clinical outcomes for multiple tumours. However, only a subset of patients achieves durable responses, suggesting that the mech...
AcetylationCancerCancer immunotherapyTumour immunology
10.1038/S41556-020-0562-4
ISSN:1465-7392
Mutations in BRCA1 and BRCA2 differentially affect the tumor microenvironment and response to checkpoint blockade immunotherapy
Robert M. Samstein•Chirag Krishna•Xiaoxiao Ma•Xin Pei•Ken-Wing Lee等 28 人
Nature Cancer
2020
•2020/11/16
•Vol.1 No.12 p.1188-1203
Immune checkpoint blockade (ICB) has improved outcomes for patients with advanced cancer, but the determinants of response remain poorly understood. Here we report differential effects of mutations in the homologous recombination genes BRCA1 and BRCA2 on response to ICB in mouse and human tumors, an...
Cancer geneticsCancer genomicsHomologous recombinationImmunogeneticsTumour immunology
10.1038/S43018-020-00139-8
ISSN:2662-1347
Downregulation of the FTO m6A RNA demethylase promotes EMT-mediated progression of epithelial tumors and sensitivity to Wnt inhibitors
Jana Jeschke•Evelyne Collignon•Clémence Al Wardi•Mohammad Krayem•Martin Bizet等 38 人
Nature Cancer
2021
•2021/6/23
•Vol.2 No.6 p.611-628
Post-transcriptional modifications of RNA constitute an emerging regulatory layer of gene expression. The demethylase fat mass- and obesity-associated protein (FTO), an eraser of N6-methyladenosine (m6A), has been shown to play a role in cancer, but its contribution to tumor progression and the unde...
CancerCell signallingEpithelial–mesenchymal transitionRNA metabolism
10.1038/S43018-021-00223-7
ISSN:2662-1347
Neutral tumor evolution?
Maxime Tarabichi•Iñigo Martincorena•Moritz Gerstung•Armand M. Leroi•Florian Markowetz
Nature Genetics
2018
•2018/10/29
•Vol.50 No.12 p.1630-1633
CancerComputational biology and bioinformaticsGenomicsMathematics and computing
10.1038/S41588-018-0258-X
ISSN:1061-4036
The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer
Patel Saroor A.•Hirosue Shoko•Rodrigues Paulo•Vojtasova Erika•Richardson Emma K.等 27 人
Nature
2022
•2022/6/8
•00 p.1-8
Large-scale human genetic data1–3 have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box...
Cancer genomicsCancer modelsFunctional genomicsGene regulationRenal cell carcinoma
10.1038/S41586-022-04809-8
ISSN:0028-0836
Deficiency in fibroblast PPARβ/δ reduces nonmelanoma skin cancers in mice
Mark Wei Yi Tan•Ming Keat Sng•Hong Sheng Cheng•Zun Siong Low•Benjamin Jia Juin Leong等 14 人
Cell Death & Differentiation
2020
•2020/4/20
•Vol.27 No.9 p.2668-2680
The incidence of nonmelanoma skin cancer (NMSC) has been increasing worldwide. Most studies have highlighted the importance of cancer-associated fibroblasts (CAFs) in NMSC progression. However much less is known about the communication between normal fibroblasts and epithelia; disruption of this com...
Cancer microenvironmentOncogenes
10.1038/S41418-020-0535-Y
ISSN:1350-9047
Global computational alignment of tumor and cell line transcriptional profiles
Allison Warren•Yejia Chen•Andrew Jones•Tsukasa Shibue•William C. Hahn等 9 人
Nature Communications
2021
•2021/1/4
•Vol.12 No.1 p.1-12
Cell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Direct comparisons of tumor and cell line transcriptional profiles are complicated by several factors, including the variable presence of normal cells in tumor samples. We ...
Cancer genomicsCancer modelsData integration
10.1038/S41467-020-20294-X
ISSN:2041-1723
Evidential deep learning-based ALK-expression screening using H&E-stained histopathological images
Sai Chandra Kosaraju•Sai Phani Parsa•Dae Hyun Song•Hyo Jung An•Yoon-La Choi等 8 人
Npj Digital Medicine
2025
•2025/10/14
•Vol.8 No.1 p.1-10
Efficient and accurate identification of genetic alterations of non-small cell lung cancer is a critical diagnostic process for targeted therapies. Utilizing advanced modern deep learning is a potential solution that can accurately predict genetic alterations from H&E-stained pathological images...
Cancer geneticsCancer imagingMachine learning
10.1038/S41746-025-01981-9
ISSN:2398-6352
Molecular and functional landscape of malignant serous effusions for precision oncology
Rebekka Wegmann•Lorenz Bankel•Yasmin Festl•Kate Lau•Sohyon Lee等 17 人
Nature Communications
2024
•2024/10/2
•Vol.15 No.1 p.1-21
Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional lev...
Cancer therapyData integrationPhenotypic screeningSingle-cell imaging
10.1038/S41467-024-52694-8
ISSN:2041-1723
Microbial gene expression analysis of healthy and cancerous esophagus uncovers bacterial biomarkers of clinical outcomes
Daniel E. Schäffer•Wenrui Li•Abdurrahman Elbasir•Dario C. Altieri•Qi Long等 6 人
Isme Communications
2023
•2023/12/5
•Vol.3 No.1 p.1-11
Local microbiome shifts are implicated in the development and progression of gastrointestinal cancers, and in particular, esophageal carcinoma (ESCA), which is among the most aggressive malignancies. Short-read RNA sequencing (RNAseq) is currently the leading technology to study gene expression chan...
Gastrointestinal diseasesMicrobiology
10.1038/S43705-023-00338-1
ISSN:2730-6151
Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways
Xiangqi Meng•Yu Zhao•Bo Han•Caijun Zha•Yangong Zhang等 11 人
Nature Communications
2020
•2020/1/30
•Vol.11 No.1 p.1-15
Activation of receptor tyrosine kinase (RTK) protein is frequently observed in malignant progression of gliomas. In this study, the crosstalk activation of epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) signaling pathways is demonstrated to contribute to t...
Biomedical materialsCNS cancerTargeted therapies
10.1038/S41467-019-14036-X
ISSN:2041-1723
LKB1 inactivation modulates chromatin accessibility to drive metastatic progression
Pierce Sarah E.•Granja Jeffrey M.•Corces M. Ryan•Brady Jennifer J.•Tsai Min K.等 13 人
Nature Cell Biology
2021
•2021/8/2
•Vol.23 No.8 p.915-924
Metastasis is the leading cause of cancer-related deaths and enables cancer cells to compromise organ function by expanding in secondary sites. Since primary tumours and metastases often share the same constellation of driver mutations, the mechanisms that drive their distinct phenotypes are unclear...
Cancer epigeneticsFunctional genomicsLung cancerMetastasis
10.1038/S41556-021-00728-4
ISSN:1465-7392
Parallel and convergent dynamics in the evolution of primary breast and lung adenocarcinomas
Robert A. Gatenby•Jamie K. Teer•Kenneth Y. Tsai•Joel S. Brown
Communications Biology
2025
•2025/5/21
•Vol.8 No.1 p.1-14
Cancer development requires an evolutionary transformation from mammalian cells fully regulated by and integrated into multicellular tissue to cancer cells that, as single cell protists, are individually subject to Darwinian selection. Through genetic and epigenetic mechanisms o...
Cancer modelsEvolutionary theory
10.1038/S42003-025-08123-7
ISSN:2399-3642
Ferroptosis-activating metabolite acrolein antagonizes necroptosis and anti-cancer therapeutics
Hyun Bae•Seonghyun Moon•Mengmeng Chang•Fenfen Zhang•Yeonseo Jang等 15 人
Nature Communications
2025
•2025/5/27
•Vol.16 No.1 p.1-17
Dysregulated cell death leading to uncontrolled cell proliferation is a hallmark of cancer. Chemotherapy-induced cell death is critical for the success of cancer treatment but this process is impaired by metabolic byproducts. How these byproducts interfere with anti-cancer therapy is unclear. Here, ...
Cancer metabolismChemotherapyNecroptosis
10.1038/S41467-025-60226-1
ISSN:2041-1723
A systematic approach to orient the human protein–protein interaction network
Dana Silverbush•Roded Sharan
Nature Communications
2019
•2019/7/9
•Vol.10 No.1 p.1-9
The protein-protein interaction (PPI) network of an organism serves as a skeleton for its signaling circuitry, which mediates cellular response to environmental and genetic cues. Understanding this circuitry could improve the prediction of gene function and cellular behavior in response to diverse s...
Cell signallingCellular signalling networksProtein analysis
10.1038/S41467-019-10887-6
ISSN:2041-1723
A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer
Jessica L. Chitty•Michelle Yam•Lara Perryman•Amelia L. Parker•Joanna N. Skhinas等 52 人
Nature Cancer
2023
•2023/8/28
•00 p.1-19
The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-55...
CancerCancer therapy
10.1038/S43018-023-00614-Y
ISSN:2662-1347
MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
Enkhtsetseg Munkhbaatar•Michelle Dietzen•Deepti Agrawal•Martina Anton•Moritz Jesinghaus等 37 人
Nature Communications
2020
•2020/9/10
•Vol.11 No.1 p.1-13
Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role o...
Non-small-cell lung cancer
10.1038/S41467-020-18372-1
ISSN:2041-1723
Hypoxia-induced exosomal LUCAT1 promotes osimertinib resistance in lung adenocarcinoma by stabilizing c-MET
Jianting Du•Bin Zheng•Jiekun Qian•Guanglei Huang•Wenjie Yuan等 13 人
Cell Death & Disease
2025
•2025/10/27
•Vol.16 No.1 p.1-16
Osimertinib resistance poses a major challenge in treating advanced EGFR-mutant lung adenocarcinoma (LUAD). Exosomes, key mediators of intercellular communication, may contribute to drug resistance, but their specific role in osimertinib resistance remains unclear. This study aimed to elucidate the ...
Non-small-cell lung cancerPredictive markers
10.1038/S41419-025-08100-2
ISSN:2041-4889
Adoptively transferred tumor-specific IL-9-producing cytotoxic CD8+ T cells activate host CD4+ T cells to control tumors with antigen loss
Liuling Xiao•Rui Duan•Wendao Liu•Chuanchao Zhang•Xingzhe Ma等 17 人
Nature Cancer
2025
•2025/4/3
•00 p.1-18
Host effector CD4+ T cells emerge as critical mediators for tumor regression but whether they can be activated by adoptively transferred CD8+ T cells remains unknown. We previously reported that adoptive transfer of interleukin 9 (IL-9)-producing cytotoxic CD8+ T (Tc9) cells achieved long-term contr...
CancerCancer immunotherapyImmunotherapyT cells
10.1038/S43018-025-00935-0
ISSN:2662-1347
Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response
Lianmei Tan•Tao Yin•Handan Xiang•Liuyang Wang•Poorva Mudgal等 20 人
Nature Communications
2024
•2024/10/3
•Vol.15 No.1 p.1-15
Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic regulator ubiquitin-like with PHD and ri...
Antigen presentationCancer microenvironmentTumour immunologyUbiquitylation
10.1038/S41467-024-52902-5
ISSN:2041-1723
NAT10-mediated mRNA N4-acetylcytidine reprograms serine metabolism to drive leukaemogenesis and stemness in acute myeloid leukaemia
Subo Zhang•Feng Huang•Yushuai Wang•Yifei Long•Yuanpei Li等 31 人
Nature Cell Biology
2024
•2024/11/6
•00 p.1-15
RNA modification has emerged as an important epigenetic mechanism that controls abnormal metabolism and growth in acute myeloid leukaemia (AML). However, the roles of RNA N4-acetylcytidine (ac4C) modification in AML remain elusive. Here, we report that ac4C and its catalytic enzyme NAT10 drive leuka...
Cancer epigeneticsCancer metabolismCancer stem cells
10.1038/S41556-024-01548-Y
ISSN:1465-7392
A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1
Ling Hai•Dirk C. Hoffmann•Robin J. Wagener•Daniel D. Azorin•David Hausmann等 31 人
Nature Communications
2024
•2024/2/6
•Vol.15 No.1 p.1-29
Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging and the impact on patient survival unresolved. Here, we establish a connectivity s...
Cancer genomicsCNS cancerGenetics researchMolecular neuroscienceTumour biomarkers
10.1038/S41467-024-45067-8
ISSN:2041-1723
An extended APOBEC3A mutation signature in cancer
Adam Langenbucher•Danae Bowen•Ramin Sakhtemani•Elodie Bournique•Jillian F. Wise等 9 人
Nature Communications
2021
•2021/3/11
•Vol.12 No.1 p.1-11
APOBEC mutagenesis, a major driver of cancer evolution, is known for targeting TpC sites in DNA. Recently, we showed that APOBEC3A (A3A) targets DNA hairpin loops. Here, we show that DNA secondary structure is in fact an orthogonal influence on A3A substrate optimality and, surprisingly, can overrid...
Cancer genomicsDNA
10.1038/S41467-021-21891-0
ISSN:2041-1723
The dopamine transporter antagonist vanoxerine inhibits G9a and suppresses cancer stem cell functions in colon tumors
Christopher J. Bergin•Aïcha Zouggar•Amanda Mendes da Silva•Tanguy Fenouil•Joshua R. Haebe等 13 人
Nature Cancer
2024
•2024/2/13
•00 p.1-18
Cancer stem cells (CSCs), functionally characterized by self-renewal and tumor-initiating activity, contribute to decreased tumor immunogenicity, while fostering tumor growth and metastasis. Targeting G9a histone methyltransferase (HMTase) effectively blocks CSC functions in colorectal tumors by alt...
CancerCancer stem cellsColon cancerDrug development
10.1038/S43018-024-00727-Y
ISSN:2662-1347
Microenvironment-triggered multimodal precision diagnostics
Liangliang Hao•Nazanin Rohani•Renee T. Zhao•Emilia M. Pulver•Howard Mak等 10 人
Nature Materials
2021
•2021/7/15
•00 p.1-9
Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization and the opportunity to monitor response to therapy. Here, we report a multimodal nanosensor engineered to target tumours through acidosis, respond to proteases in the microenvironment to r...
BiotechnologyCancerEngineeringMaterials scienceNanoscience and technology
10.1038/S41563-021-01042-Y
ISSN:1476-1122
Estimating the predictive power of silent mutations on cancer classification and prognosis
Gutman Tal•Goren Guy•Efroni Omri•Tuller Tamir
Npj Genomic Medicine
2021
•2021/8/12
•Vol.6 No.1 p.1-15
In recent years it has been shown that silent mutations, in and out of the coding region, can affect gene expression and may be related to tumorigenesis and cancer cell fitness. However, the predictive ability of these mutations for cancer type diagnosis and prognosis has not been evaluated yet. In ...
Gene expressionGenome informaticsPredictive markersSystems biology
10.1038/S41525-021-00229-1
ISSN:2056-7944
Wnt-deficient and hypoxic environment orchestrates squamous reprogramming of human pancreatic ductal adenocarcinoma
Hiroki Tamagawa•Masayuki Fujii•Kazuhiro Togasaki•Takashi Seino•Shintaro Kawasaki等 25 人
Nature Cell Biology
2024
•2024/9/4
•00 p.1-14
Human pancreatic cancer is characterized by the molecular diversity encompassing native duct-like and squamous cell-like identities, but mechanisms underlying squamous transdifferentiation have remained elusive. To comprehensively capture the molecular diversity of human pancreatic cancer, we here p...
Cancer epigeneticsCancer microenvironmentPancreatic cancer
10.1038/S41556-024-01498-5
ISSN:1465-7392
Targeting tumor-intrinsic BCL9 reverses immunotherapy resistance by eliciting macrophage-mediated phagocytosis and antigen presentation
Sui-Yi Wu•Yuan-Yuan Zhu•Jia-Lei Sun•Chun-Yan Wang•Yu-Lei Wang等 20 人
Nature Communications
2025
•2025/11/17
•Vol.16 No.1 p.100390
Immune checkpoint inhibitors (ICI) benefit some cancer patients but de novo resistance remains poorly understood. Analyzing transcriptional data from two clinical trial cohorts, GO30140 and IMbrave150, we find B cell lymphoma 9 (BCL9), a Wnt/β-catenin co-factor, associated with resistance. We develo...
Cancer immunotherapyCancer therapeutic resistanceImmunosurveillanceLiver cancerMonocytes and macrophages
10.1038/S41467-025-65945-Z
ISSN:2041-1723
miR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma
Wen Cai Zhang•Julie M. Wells•Kin-Hoe Chow•He Huang•Min Yuan等 12 人
Nature Metabolism
2019
•2019/4/8
•Vol.1 No.4 p.460-474
Drug tolerance is an acute defence response preceding a fully drug-resistant state and tumour relapse; however, there are few therapeutic agents targeting drug tolerance in the clinic. Here we show that miR-147b initiates a reversible state of tolerance to the epidermal growth factor receptor (EGFR)...
Cancer metabolismNon-small-cell lung cancer
10.1038/S42255-019-0052-9
ISSN:2522-5812
Pparg signaling controls bladder cancer subtype and immune exclusion
Tate Tiffany•Xiang Tina•Wobker Sarah E.•Zhou Mi•Chen Xiao等 12 人
Nature Communications
2021
•2021/10/25
•Vol.12 No.1 p.1-14
Pparg, a nuclear receptor, is downregulated in basal subtype bladder cancers that tend to be muscle invasive and amplified in luminal subtype bladder cancers that tend to be non-muscle invasive. Bladder cancers derive from the urothelium, one of the most quiescent epithelia in the body, which is com...
Bladder cancerCancer modelsTumour heterogeneity
10.1038/S41467-021-26421-6
ISSN:2041-1723
Inferring early genetic progression in cancers with unobtainable premalignant disease
Leshchiner Ignaty•Mroz Edmund A.•Cha Justin•Rosebrock Daniel•Spiro Oliver等 12 人
Nature Cancer
2023
•2023/4/20
•00 p.1-14
Analysis of premalignant tissue has identified the typical order of somatic events leading to invasive tumors in several cancer types. For other cancers, premalignant tissue is unobtainable, leaving genetic progression unknown. Here, we demonstrate how to infer progression from exome sequencing of p...
CancerCancer genomicsComputational biology and bioinformaticsHead and neck cancer
10.1038/S43018-023-00533-Y
ISSN:2662-1347
Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation
Elizabeth J. Radford•Hong-Kee Tan•Malin H. L. Andersson•James D. Stephenson•Eugene J. Gardner等 19 人
Nature Communications
2023
•2023/12/6
•Vol.14 No.1 p.1-17
Loss-of-function of DDX3X is a leading cause of neurodevelopmental disorders (NDD) in females. DDX3X is also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We perform saturation genome editing of DDX3X, testing in vitro the functional impact of 12...
Cancer geneticsMutagenesisMutationNeurodevelopmental disorders
10.1038/S41467-023-43041-4
ISSN:2041-1723
Dual modulation of cytotoxic and checkpoint receptors tunes the efficacy of adoptive Delta One T cell therapy against colorectal cancer
Rafael Blanco-Domínguez•Leandro Barros•Mariana Carreira•Manon van der Ploeg•Carolina Condeço等 13 人
Nature Cancer
2025
•2025/4/16
•00 p.1-17
Colorectal cancer (CRC) remains a challenge for current immunotherapies. Vδ1+ γδ T cells offer a promising alternative because of their HLA-I-independent cytotoxicity and natural tissue tropism. We developed Delta One T (DOT) cells, a Vδ1+ γδ T cell-based adoptive cell therapy clinically explored fo...
CancerColorectal cancerImmunotherapyTumour immunology
10.1038/S43018-025-00948-9
ISSN:2662-1347
Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome
Bengi Ruken Yavuz•M. Kaan Arici•Habibe Cansu Demirel•Chung-Jung Tsai•Hyunbum Jang等 7 人
Npj Genomic Medicine
2023
•2023/11/4
•Vol.8 No.1 p.1-14
Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, a...
Computational biology and bioinformaticsSystems biology
10.1038/S41525-023-00377-6
ISSN:2056-7944
Deubiquitination enzyme USP35 negatively regulates MAVS signaling to inhibit anti-tumor immunity
Heping Zhang•Jiali Zhu•Rong He•Lin Xu•Yunfei Chen等 15 人
Cell Death & Disease
2025
•2025/2/27
•Vol.16 No.1 p.1-12
The RIG-I/MAVS signaling stimulates anti-tumor immunity by triggering the production of inflammatory cytokines. Activation of MAVS induced by viral RNA and RIG-I binding is critical in this pathway. However, the molecular mechanism underlying the regulation of MAVS activity and its function in anti-...
Cancer microenvironmentCancer therapy
10.1038/S41419-025-07411-8
ISSN:2041-4889
Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis
Lifu Luo•Qingzhi Zhao•Xueli Cui•Shijiao Dong•Yong Wang等 9 人
Cell Death & Disease
2025
•2025/4/12
•Vol.16 No.1 p.1-12
MSL1, a scaffold protein of the MSL histone acetyltransferase complex, is crucial for its structural integrity and enzymatic activity. While MSL1 is highly expressed in various tumors, its role in tumor progression and cell death remains unclear. Here, we provide evidence of a negative regulatory re...
Colon cancerPreclinical research
10.1038/S41419-025-07555-7
ISSN:2041-4889
HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors
Kwon-Ho Song•Se Jin Oh•Suyeon Kim•Hanbyoul Cho•Hyo-Jung Lee等 16 人
Nature Communications
2020
•2020/1/28
•Vol.11 No.1 p.1-16
Cancer immunotherapy has emerged as a promising cancer treatment. However, the presence of immune-refractory tumor cells limits its clinical success by blocking amplification of anti-tumor immunity. Previously, we found that immune selection by immunotherapy drives the evolution of tumors toward mul...
CancerCancer stem cellsCancer therapyTumour immunology
10.1038/S41467-019-14259-Y
ISSN:2041-1723
Aberrant PJA2-CHRM3 signaling creates a therapeutic vulnerability in gastric tumor
Lingmeng Li•Jingyi Yin•Ling Zhang•Wenshuai Liu•Yinan Niu等 14 人
British Journal Of Cancer
2025
•2025/8/26
•00 p.1-15
Vagal innervation plays a pivotal role in gastric tumorigenesis and tumor progression. However, the upstream signaling regulating acetylcholine receptors (AChRs) and its contribution to carcinogenesis remains largely elusive. We constructed Trp53−/−; Cdh1−/− mouse gastric organoids to recapitulate t...
Gastric cancerUbiquitylation
10.1038/S41416-025-03145-8
ISSN:0007-0920
The metabolic landscape of RAS-driven cancers from biology to therapy
Suman Mukhopadhyay•Matthew G. Vander Heiden•Frank McCormick
Nature Cancer
2021
•2021/3/24
•Vol.2 No.3 p.271-283
Our understanding of how the RAS protein family, and in particular mutant KRAS, promotes metabolic dysregulation in cancer cells has advanced substantially over the last decade. In this Review, we discuss the metabolic reprogramming mediated by oncogenic RAS in cancer and elucidate the underlying me...
Cancer metabolismOncogenes
10.1038/S43018-021-00184-X
ISSN:2662-1347
CRISPR screens decode cancer cell pathways that trigger γδ T cell detection
Murad R. Mamedov•Shane Vedova•Jacob W. Freimer•Avinash Das Sahu•Amrita Ramesh等 18 人
Nature
2023
•2023/8/30
•00 p.1-8
γδ T cells are potent anticancer effectors with the potential to target tumours broadly, independent of patient-specific neoantigens or human leukocyte antigen background1–5. γδ T cells can sense conserved cell stress signals prevalent in transformed cells2,3, although the mechanisms behind the targ...
Cancer metabolismGammadelta T cellsImmunosurveillance
10.1038/S41586-023-06482-X
ISSN:0028-0836
Integrating molecular profiles into clinical frameworks through the Molecular Oncology Almanac to prospectively guide precision oncology
Reardon Brendan•Moore Nathanael D.•Moore Nicholas S.•Kofman Eric•AlDubayan Saud H.等 19 人
Nature Cancer
2021
•2021/9/30
•00 p.1-11
Tumor molecular profiling of single gene-variant (‘first-order’) genomic alterations informs potential therapeutic approaches. Interactions between such first-order events and global molecular features (for example, mutational signatures) are increasingly associated with clinical outcomes, but these...
CancerCancer genomicsSoftware
10.1038/S43018-021-00243-3
ISSN:2662-1347
Pan-cancer analysis of mRNA stability for decoding tumour post-transcriptional programs
Perron Gabrielle•Jandaghi Pouria•Moslemi Elham•Nishimura Tamiko•Rajaee Maryam等 9 人
Communications Biology
2022
•2022/8/20
•Vol.5 No.1 p.1-14
Measuring mRNA decay in tumours is a prohibitive challenge, limiting our ability to map the post-transcriptional programs of cancer. Here, using a statistical framework to decouple transcriptional and post-transcriptional effects in RNA-seq data, we uncover the mRNA stability changes that accompany ...
Cancer genomicsGene regulatory networksRegulatory networksTranscriptomics
10.1038/S42003-022-03796-W
ISSN:2399-3642
Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma
Rached Alkallas•Mathieu Lajoie•Dan Moldoveanu•Karen Vo Hoang•Philippe Lefrançois等 12 人
Nature Cancer
2020
•2020/6/22
•Vol.1 No.6 p.635-652
The high background tumor mutation burden in cutaneous melanoma limits the ability to identify significantly mutated genes (SMGs) that drive this cancer. To address this, we performed a mutation significance study of over 1,000 melanoma exomes, combined with a multi-omic analysis of 470 cases from T...
CancerCancer genomicsMelanoma
10.1038/S43018-020-0077-8
ISSN:2662-1347
Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas
Salvador Polo-Generelo•Cristina Rodríguez-Mateo•Belén Torres•José Pintor-Tortolero•José A. Guerrero-Martínez等 12 人
Cell Death Discovery
2024
•2024/3/6
•Vol.10 No.1 p.1-14
Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, indepen...
Colon cancerImmune evasionImmunosurveillanceLong non-coding RNAs
10.1038/S41420-024-01886-8
ISSN:2058-7716
AAK1 activation-mediated iron trafficking drives ferroptotic cell death
Li-Chao Li•Zhi-Peng Ye•Ying Xiao•Xian-Ying Zhu•Qia-Qia Li等 20 人
Nature Communications
2025
•2025/12/17
0Ferrous iron is necessary for the occurrence of ferroptosis. The molecular mechanisms that maintain iron homeostasis within cells play a crucial role in the regulation of ferroptosis. However, how cells regulate iron uptake during ferroptosis remains unclear. Here, PKCβII is identified as a key kina...
Cell deathMolecular medicinePost-translational modifications
10.1038/S41467-025-67523-9
ISSN:2041-1723
Classification and mutation prediction based on histopathology H&E images in liver cancer using deep learning
Mingyu Chen•Bin Zhang•Win Topatana•Jiasheng Cao•Hepan Zhu等 9 人
Npj Precision Oncology
2020
•2020/6/8
•Vol.4 No.1 p.1-7
Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, and assessing its histopathological grade requires visual inspection by an experienced pathologist. In this study, the histopathological H&E images from the Genomic Data Commons Databases were used to train a neural network (...
Cancer imagingCancer modelsHepatocellular carcinoma
10.1038/S41698-020-0120-3
ISSN:2397-768X
Identification of hyper-rewired genomic stress non-oncogene addiction genes across 15 cancer types
Jessica Xin Hjaltelin•Jose M. G. Izarzugaza•Lars Juhl Jensen•Francesco Russo•David Westergaard等 6 人
Npj Systems Biology And Applications
2019
•2019/8/7
•Vol.5 No.1 p.1-10
Non-oncogene addiction (NOA) genes are essential for supporting the stress-burdened phenotype of tumours and thus vital for their survival. Although NOA genes are acknowledged to be potential drug targets, there has been no large-scale attempt to identify and characterise them as a group across canc...
CancerComputational biology and bioinformatics
10.1038/S41540-019-0104-5
ISSN:2056-7189
EGFRvIII-positive glioblastoma contributes to immune escape and malignant progression via the c-Fos-MDK-LRP1 axis
Feng Yuan•Yingshuai Wang•Lei Yuan•Ting Tang•Lei Ye等 8 人
Cell Death & Disease
2025
•2025/6/17
•Vol.16 No.1 p.1-16
Epidermal growth factor receptor variant III (EGFRvIII) confers growth advantage to glioblastoma multiforme (GBM) and is associated with significantly shorter survival in GBM patients. The interaction between tumor cells and macrophages plays a crucial role in tumor development, supporting angiogene...
Cancer microenvironmentCNS cancer
10.1038/S41419-025-07771-1
ISSN:2041-4889
USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma
Ning Zhen•Guo Xin•Liu Xiaolong•Lu Chang•Wang Aman等 23 人
Nature Communications
2022
•2022/4/21
•Vol.13 No.1 p.1-18
Elevated de novo lipogenesis is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. Herein, we identify ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with deubiquitinates and stabilizes peroxisome pro...
CancerCancer metabolism
10.1038/S41467-022-29846-9
ISSN:2041-1723
Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis
Ute Jungwirth•Antoinette van Weverwijk•Rachel J. Evans•Liam Jenkins•David Vicente等 10 人
Nature Communications
2021
•2021/6/10
•Vol.12 No.1 p.1-17
Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show...
Breast cancerCancer microenvironmentMechanisms of diseaseMetastasis
10.1038/S41467-021-23583-1
ISSN:2041-1723
Progressive senescence programs induce intrinsic vulnerability to aging-related female breast cancer
Huiru Bai•Xiaoqin Liu•Meizhen Lin•Yuan Meng•Ruolan Tang等 9 人
Nature Communications
2024
•2024/6/17
•Vol.15 No.1 p.1-19
Cancer incidence escalates exponentially with advancing age; however, the underlying mechanism remains unclear. In this study, we build a chronological molecular clock at single-cell transcription level with a mammary stem cell-enriched population to depict physiological aging dynamics in female mic...
Breast cancerMammary stem cellsSenescence
10.1038/S41467-024-49106-2
ISSN:2041-1723
Proteolysis activity mapping and substrate discovery platform for identifying tumor-activated biosensors
Itay Algov•Audrey Van Heest•Megan Hopton•Frances Liang•Aidan Holmes等 7 人
Nature Chemical Biology
2026
•2026/5/11
•00 p.1-14
Dysregulated extracellular proteolytic activity is a prominent hallmark of cancer and can thus be exploited for tumor detection and therapeutic development. However, the discovery of tumor-responsive probes has been hindered by the lack of methods to directly screen proteolytic events in specific ti...
Combinatorial librariesProteasesSynthetic biology
10.1038/S41589-026-02218-W
ISSN:1552-4450
Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer
Xiaoguang Liu•Kellen Olszewski•Yilei Zhang•Esther W. Lim•Jiejun Shi等 17 人
Nature Cell Biology
2020
•2020/3/30
•Vol.22 No.4 p.476-486
SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its low solubility, forcing cancer cells with high leve...
CancerCancer metabolismCancer therapy
10.1038/S41556-020-0496-X
ISSN:1465-7392
Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance
Hao Zheng•Jinming Liu•Qi Cheng•Qianping Zhang•Yaoyao Zhang等 22 人
Nature Cancer
2024
•2024/1/30
•00 p.1-18
Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal...
CancerGastrointestinal cancer
10.1038/S43018-023-00715-8
ISSN:2662-1347
A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures
Miklos Diossy•Zsofia Sztupinszki•Judit Borcsok•Marcin Krzystanek•Viktoria Tisza等 14 人
Npj Precision Oncology
2021
•2021/6/18
•Vol.5 No.1 p.1-8
PARP inhibitors are approved for the treatment of solid tumor types that frequently harbor alterations in the key homologous recombination (HR) genes, BRCA1/2. Other tumor types, such as lung cancer, may also be HR deficient, but the frequency of such cases is less well characterized. Specific DNA a...
Non-small-cell lung cancer
10.1038/S41698-021-00199-8
ISSN:2397-768X
Synthetic lethality of RB1 and aurora A is driven by stathmin-mediated disruption of microtubule dynamics
Junfang Lyu•Eun Ju Yang•Baoyuan Zhang•Changjie Wu•Lakhansing Pardeshi等 10 人
Nature Communications
2020
•2020/10/9
•Vol.11 No.1 p.1-16
RB1 mutational inactivation is a cancer driver in various types of cancer including lung cancer, making it an important target for therapeutic exploitation. We performed chemical and genetic vulnerability screens in RB1-isogenic lung cancer pair and herein report that aurora kinase A (AURKA) inhibit...
CancerDrug discoveryMedical research
10.1038/S41467-020-18872-0
ISSN:2041-1723
TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via GSK3β/β-catenin signalling
Gao Song•Wang Shuaibin•Zhao Zhiying•Zhang Chao•Liu Zhicao等 17 人
Nature Communications
2022
•2022/5/19
•Vol.13 No.1 p.1-16
Human tubulin beta class IVa (TUBB4A) is a member of the β-tubulin family. In most normal tissues, expression of TUBB4A is little to none, but it is highly expressed in human prostate cancer. Here we show that high expression levels of TUBB4A are associated with aggressive prostate cancers and poor ...
MetastasisProstateProstate cancer
10.1038/S41467-022-30409-1
ISSN:2041-1723
Inhibition of the succinyl dehydrogenase complex in acute myeloid leukemia leads to a lactate-fuelled respiratory metabolic vulnerability
Erdem Ayşegül•Marin Silvia•Pereira-Martins Diego A.•Geugien Marjan•Cunningham Alan等 14 人
Nature Communications
2022
•2022/4/19
•Vol.13 No.1 p.1-15
Metabolic programs can differ substantially across genetically distinct subtypes of acute myeloid leukemia (AML). These programs are not static entities but can change swiftly as a consequence of extracellular changes or in response to pathway-inhibiting drugs. Here, we uncover that AML patients wit...
Cancer metabolismHaematological cancer
10.1038/S41467-022-29639-0
ISSN:2041-1723
Neutrophils physically interact with tumor cells to form a signaling niche promoting breast cancer aggressiveness
Sandra Camargo•Ori Moskowitz•Amir Giladi•Maiia Levinson•Roi Balaban等 15 人
Nature Cancer
2025
•2025/3/7
•00 p.1-19
Tissue remodeling and cell plasticity in the mammary gland are activated by multilineage communications; however, the dynamic signaling promoting breast cancer remains unclear. Here, by RNA sequencing of single cells and physically interacting cells (PICs) along mammary gland development and carcino...
Breast cancerCancerImmunologyTumour immunology
10.1038/S43018-025-00924-3
ISSN:2662-1347
VCAM1 confers innate immune tolerance on haematopoietic and leukaemic stem cells
Pinho Sandra•Wei Qiaozhi•Maryanovich Maria•Zhang Dachuan•Balandrán Juan Carlos等 13 人
Nature Cell Biology
2022
•2022/2/24
•00 p.1-9
Haematopoietic stem cells (HSCs) home to the bone marrow via, in part, interactions with vascular cell adhesion molecule-1 (VCAM1)1–3. Once in the bone marrow, HSCs are vetted by perivascular phagocytes to ensure their self-integrity. Here we show that VCAM1 is also expressed on healthy HSCs and upr...
Cancer stem cellsHaematopoietic stem cellsImmune evasion
10.1038/S41556-022-00849-4
ISSN:1465-7392
GAS41 modulates ferroptosis by anchoring NRF2 on chromatin
Zhe Wang•Xin Yang•Delin Chen•Yanqing Liu•Zhiming Li等 10 人
Nature Communications
2024
•2024/3/21
•Vol.15 No.1 p.1-16
YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recogni...
Cell deathEpigeneticsHigh-throughput screeningNon-small-cell lung cancerTranscription
10.1038/S41467-024-46857-W
ISSN:2041-1723
Specific regulation of BACH1 by the hotspot mutant p53R175H reveals a distinct gain-of-function mechanism
Su Zhenyi•Kon Ning•Yi Jingjie•Zhao Haiqing•Zhang Wanwei等 17 人
Nature Cancer
2023
•2023/3/27
•00 p.1-18
Although the gain of function (GOF) of p53 mutants is well recognized, it remains unclear whether different p53 mutants share the same cofactors to induce GOFs. In a proteomic screen, we identified BACH1 as a cellular factor that recognizes the p53 DNA-binding domain depending on its mutation status...
CancerCell deathMetastasis
10.1038/S43018-023-00532-Z
ISSN:2662-1347
A vaccine-based nanosystem for initiating innate immunity and improving tumor immunotherapy
Di-Wei Zheng•Fan Gao•Qian Cheng•Peng Bao•Xue Dong等 10 人
Nature Communications
2020
•2020/4/24
•Vol.11 No.1 p.1-15
The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanos...
Breast cancerCancer therapy
10.1038/S41467-020-15927-0
ISSN:2041-1723
MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway
Li-wen Yao•Lian-lian Wu•Li-hui Zhang•Wei Zhou•Lu Wu等 17 人
Oncogenesis
2020
•2020/2/13
•Vol.9 No.2 p.1-17
Gastric cancer (GC) is one of the most common malignancies and its prognosis is extremely poor. This study identifies a novel oncogene, microfibrillar-associated protein 2 (MFAP2) in GC. With integrative reanalysis of transcriptomic data, we found MFAP2 as a GC prognosis-related gene. And the aberra...
Cancer microenvironmentGastric cancer
10.1038/S41389-020-0198-Z
ISSN:2157-9024
Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer
Valsamo Anagnostou•Noushin Niknafs•Kristen Marrone•Daniel C. Bruhm•James R. White等 35 人
Nature Cancer
2020
•2020/1/13
•Vol.1 No.1 p.99-111
Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumor...
Cancer genomicsImmunotherapy
10.1038/S43018-019-0008-8
ISSN:2662-1347
Disruption of tRNA threonylation triggers RIG-I mediated anti-tumour immune response
Cléa Dziagwa•Christian Seca•Coralie Capron•Chloe Maurizy•Ning An等 20 人
Nature Communications
2026
•2026/2/25
•Vol.17 No.1 p.31450
Tumour-induced mechanisms of immune evasion hinder immune response to cancer, particularly in melanoma. mRNA translation, by ensuring accurate protein synthesis, regulates cancer phenotypes and immune response, but the underlying mechanisms remain unclear. Here, we reveal how O-sialoglycoprotein end...
MelanomatRNAs
10.1038/S41467-026-69964-2
ISSN:2041-1723
FOXA1-dependent NSUN2 facilitates the advancement of prostate cancer by preserving TRIM28 mRNA stability in a m5C-dependent manner
Zhenda Wang•Abudurexiti Mierxiati•Wenkai Zhu•Tian Li•Hua Xu等 7 人
Npj Precision Oncology
2025
•2025/5/3
•Vol.9 No.1 p.1-16
RNA epigenetics is gaining increased attention for its role in the initiation, metastasis, and drug resistance of tumors. These studies have primarily focused on m6A modification. However, despite being the second most abundant modification found in RNA, the role of m5C modification in prostate canc...
CancerDiseasesOncology
10.1038/S41698-025-00904-X
ISSN:2397-768X
SLC2A1+ tumour-associated macrophages spatially control CD8+ T cell function and drive resistance to immunotherapy in non-small-cell lung cancer
Lei Wang•Han Chu•Degao Chen•Yuxuan Wei•Jia Jia等 21 人
Nature Cell Biology
2026
•2026/1/7
•Vol.28 No.2 p.338-348
Tumour-associated macrophages (TAMs) contribute to immune checkpoint blockade resistance, but their impact on intratumoural CD8⁺ T cell distribution remains unclear. Here we show that the expression of the glucose transporter SLC2A1 is spatially negatively correlated with CD8⁺ T cell distribution in...
Monocytes and macrophagesNon-small-cell lung cancerT cellsTumour immunology
10.1038/S41556-025-01840-5
ISSN:1465-7392
SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis
Guihua Wang•Jie Long•Yuan Gao•Weina Zhang•Fei Han等 19 人
Nature Cell Biology
2019
•2019/1/28
•Vol.21 No.2 p.214-225
The serine/threonine kinase Akt plays a central role in cell proliferation, survival and metabolism, and its hyperactivation is linked to cancer progression. Here we report that Akt undergoes K64 methylation by SETDB1, which is crucial for cell membrane recruitment, phosphorylation and activation of...
CancerGrowth factor signallingMethylationUbiquitylation
10.1038/S41556-018-0266-1
ISSN:1465-7392
RNA m6A regulates transcription via DNA demethylation and chromatin accessibility
Deng Shuang•Zhang Jialiang•Su Jiachun•Zuo Zhixiang•Zeng Lingxing等 21 人
Nature Genetics
2022
•2022/9/7
•Vol.54 No.9 p.1427-1437
Transcriptional regulation, which integrates chromatin accessibility, transcription factors and epigenetic modifications, is crucial for establishing and maintaining cell identity. The interplay between different epigenetic modifications and its contribution to transcriptional regulation remains elu...
EpigeneticsGene regulationOesophageal cancer
10.1038/S41588-022-01173-1
ISSN:1061-4036
EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1
Wang Jie•Ge Junshang•Wang Yian•Xiong Fang•Guo Jiayue等 22 人
Nature Communications
2022
•2022/2/14
•Vol.13 No.1 p.1-21
Epstein-Barr virus (EBV) is reportedly the first identified human tumor virus, and is closely related to the occurrence and development of nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and several lymphomas. PD-L1 expression is elevated in EBV-positive NPC and GC tissues; however, the spec...
Cancer epigeneticsImmunoeditingTumour virus infections
10.1038/S41467-022-28479-2
ISSN:2041-1723
Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer
Luigi Perelli•Federica Carbone•Li Zhang•Justin K. Huang•Courtney Le等 44 人
Nature Cancer
2023
•2023/6/26
•00 p.1-17
Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR–Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver...
CancerCancer genomicsMetastasisRenal cell carcinoma
10.1038/S43018-023-00584-1
ISSN:2662-1347
CHD1 loss reprograms SREBP2-driven cholesterol synthesis to fuel androgen-responsive growth and castration resistance in SPOP-mutated prostate tumors
Feiyu Chen•Haoyan Li•Yin Wang•Ximing Tang•Kevin Lin等 21 人
Nature Cancer
2025
•2025/5/13
•00 p.1-20
Despite undergoing castration, most individuals with prostate cancer (PCa) experience progression to castration-resistant PCa (CRPC), in which the androgen receptor (AR) remains an important driver. Concurrent genetic alterations in SPOP and CHD1 define a unique subtype of PCa, but their interaction...
CancerCancer geneticsCancer metabolismCancer therapeutic resistanceProstate cancer
10.1038/S43018-025-00952-Z
ISSN:2662-1347
DNA methylation-based classification of sinonasal tumors
Jurmeister Philipp•Glöß Stefanie•Roller Renée•Leitheiser Maximilian•Schmid Simone等 66 人
Nature Communications
2022
•2022/11/28
•Vol.13 No.1 p.1-14
The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation pattern...
DNA methylationHead and neck cancerMachine learningProteomics
10.1038/S41467-022-34815-3
ISSN:2041-1723
CRISPR-Cas-amplified urinary biomarkers for multiplexed and portable cancer diagnostics
Hao Liangliang•Zhao Renee T.•Welch Nicole L.•Tan Edward Kah Wei•Zhong Qian等 11 人
Nature Nanotechnology
2023
•2023/4/24
•00 p.1-10
Synthetic biomarkers, bioengineered sensors that generate molecular reporters in diseased microenvironments, represent an emerging paradigm in precision diagnostics. Despite the utility of DNA barcodes as a multiplexing tool, their susceptibility to nucleases in vivo has limited their utility. Here ...
Biomedical engineeringBiosensors
10.1038/S41565-023-01372-9
ISSN:1748-3387
Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis
Kohei Saeki•Gregory Chang•Noriko Kanaya•Xiwei Wu•Jinhui Wang等 9 人
Communications Biology
2021
•2021/6/2
•Vol.4 No.1 p.1-16
The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained b...
Breast cancerData integrationDifferentiation
10.1038/S42003-021-02201-2
ISSN:2399-3642
Ageing promotes metastasis via activation of the integrated stress response
Angana A. H. Patel•Jozefina J. Dzanan•Kevin X. Ali•Ella A. Eklund•Samantha W. Alvarez等 29 人
Nature
2026
•2026/3/11
•00 p.1-10
Lung cancer predominantly affects older individuals, yet how physiological ageing influences tumour evolution remains poorly understood1. Here we show that ageing reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumour growth while promoting metastatic diss...
AgeingCancer metabolismMechanisms of diseaseMetastasisNon-small-cell lung cancer
10.1038/S41586-026-10216-0
ISSN:0028-0836
Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer
Irati Macaya•Marta Roman•Connor Welch•Rodrigo Entrialgo-Cadierno•Marina Salmon等 32 人
Nature Communications
2023
•2023/10/10
•Vol.14 No.1 p.1-19
Drug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS pro...
CancerLung cancerTargeted therapies
10.1038/S41467-023-41828-Z
ISSN:2041-1723
Hypoxia-induced XBP1s-MYDGF axis suppresses ferroptosis through UBQLN1-mediated stabilization of LCN2 in gastric cancer
Qi Zhou•Hongyan Qi•Yonghui Zou•Zhenqi Yue•Jinheng Gan等 9 人
Oncogene
2026
•2026/4/7
•00 p.1-14
Solid tumors such as gastric cancers exploit hypoxia-induced adaptive mechanisms to evade cell death. Here, we identify a hypoxia-triggered signaling axis in which the spliced form of XBP1s transcriptionally activates MYDGF. We demonstrate that MYDGF competitively binds the ubiquitin adaptor protein...
Cell deathGastrointestinal cancer
10.1038/S41388-026-03760-6
ISSN:0950-9232
Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms
Lehtiö Janne•Arslan Taner•Siavelis Ioannis•Pan Yanbo•Socciarelli Fabio等 29 人
Nature Cancer
2021
•2021/11/22
•Vol.2 No.11 p.1224-1242
Despite major advancements in lung cancer treatment, long-term survival is still rare and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune-evasion mechanisms. Here we performed in-depth mass-spectrometry-based proteogenomic anal...
Mass spectrometryNon-small-cell lung cancerSystems analysisTumour biomarkers
10.1038/S43018-021-00259-9
ISSN:2662-1347
Germline rare deleterious variant load alters cancer risk, age of onset and tumor characteristics
Esai Selvan Myvizhi•Onel Kenan•Gnjatic Sacha•Klein Robert J.•Gümüş Zeynep H.
Npj Precision Oncology
2023
•2023/1/27
•Vol.7 No.1 p.1-12
Recent studies show that rare, deleterious variants (RDVs) in certain genes are critical determinants of heritable cancer risk. To more comprehensively understand RDVs, we performed the largest-to-date germline variant calling analysis in a case-control setting for a multi-cancer association study f...
Cancer geneticsCancer genomicsRisk factors
10.1038/S41698-023-00354-3
ISSN:2397-768X
TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt/β-catenin signalling
Youn-Sang Jung•Sohee Jun•Moon Jong Kim•Sung Ho Lee•Han Na Suh等 18 人
Nature Cell Biology
2018
•2018/10/29
•Vol.20 No.12 p.1421-1433
Vesicular acidification and trafficking are associated with various cellular processes. However, their pathologic relevance to cancer remains elusive. We identified transmembrane protein 9 (TMEM9) as a vesicular acidification regulator. TMEM9 is highly upregulated in colorectal cancer. Proteomic and...
CancerColorectal cancerOncogenes
10.1038/S41556-018-0219-8
ISSN:1465-7392
A deep learning approach reveals unexplored landscape of viral expression in cancer
Elbasir Abdurrahman•Ye Ying•Schäffer Daniel E.•Hao Xue•Wickramasinghe Jayamanna等 12 人
Nature Communications
2023
•2023/2/11
•Vol.14 No.1 p.1-12
About 15% of human cancer cases are attributed to viral infections. To date, virus expression in tumor tissues has been mostly studied by aligning tumor RNA sequencing reads to databases of known viruses. To allow identification of divergent viruses and rapid characterization of the tumor virome, we...
CancerComputational biology and bioinformatics
10.1038/S41467-023-36336-Z
ISSN:2041-1723
LobSig is a multigene predictor of outcome in invasive lobular carcinoma
Amy E. McCart Reed•Samir Lal•Jamie R. Kutasovic•Leesa Wockner•Alan Robertson等 21 人
Npj Breast Cancer
2019
•2019/6/27
•Vol.5 No.1 p.1-11
Invasive lobular carcinoma (ILC) is the most common special type of breast cancer, and is characterized by functional loss of E-cadherin, resulting in cellular adhesion defects. ILC typically present as estrogen receptor positive, grade 2 breast cancers, with a good short-term prognosis. Several lar...
Breast cancerCancer genomics
10.1038/S41523-019-0113-Y
ISSN:2374-4677
Leucyl-tRNA synthetase is a tumour suppressor in breast cancer and regulates codon-dependent translation dynamics
Passarelli Maria C.•Pinzaru Alexandra M.•Asgharian Hosseinali•Liberti Maria V.•Heissel Søren等 8 人
Nature Cell Biology
2022
•2022/3/14
•Vol.24 No.3 p.307-315
Tumourigenesis and cancer progression require enhanced global protein translation1–3. Such enhanced translation is caused by oncogenic and tumour-suppressive events that drive the synthesis and activity of translational machinery4,5. Here we report the surprising observation that leucyl-tRNA synthet...
Breast cancerTranslationTumour-suppressor proteins
10.1038/S41556-022-00856-5
ISSN:1465-7392
CAR T cells redirected to cell surface GRP78 display robust anti-acute myeloid leukemia activity and do not target hematopoietic progenitor cells
Hebbar Nikhil•Epperly Rebecca•Vaidya Abishek•Thanekar Unmesha•Moore Sarah E.等 14 人
Nature Communications
2022
•2022/1/31
•Vol.13 No.1 p.1-14
Developing CAR T cells for acute myeloid leukemia (AML) has been hampered by a paucity of targets that are expressed on AML blasts and not on hematopoietic progenitor cells (HPCs). Here we demonstrate that GRP78 is expressed on the cell surface of primary AML blasts but not HPCs. To target GRP78, we...
Cancer immunotherapyHaematological cancerImmunotherapy
10.1038/S41467-022-28243-6
ISSN:2041-1723
CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy
Alba Rodriguez-Garcia•Rachel C. Lynn•Mathilde Poussin•Monika A. Eiva•Lauren C. Shaw等 11 人
Nature Communications
2021
•2021/2/9
•Vol.12 No.1 p.1-17
The immunosuppressive tumor microenvironment (TME) represents a major barrier for effective immunotherapy. Tumor-associated macrophages (TAMs) are highly heterogeneous and plastic cell components of the TME which can either promote tumor progression (M2-like) or boost antitumor immunity (M1-like). H...
Cancer immunotherapyCancer microenvironmentImmunotherapy
10.1038/S41467-021-20893-2
ISSN:2041-1723
CRISPR/Cas9 screening identifies SUV39H2 as a key regulator of oHSV-1 resistance in oral squamous cell carcinoma
Manman Qiu•Qicheng Zhang•Rui Li•Rongrong Wei•Jiawei Zhao等 8 人
Cell Death Discovery
2025
•2025/8/23
•Vol.11 No.1 p.1-15
Oncolytic viruses represent an innovative strategy for cancer therapy. However, extensive gene expression reprogramming within tumor cells may hinder viral propagation by affecting essential cell-virus interactions. Here, through genome-wide CRISPR/Cas9 library screening, Suppressor of variegation 3...
Oral cancerTarget validation
10.1038/S41420-025-02702-7
ISSN:2058-7716
ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer
Ines Mota•Enrico Patrucco•Cristina Mastini•Navin R. Mahadevan•Tran C. Thai等 31 人
Nature Cancer
2023
•2023/7/10
•Vol.4 No.7 p.1016-1035
Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is treated with ALK tyrosine kinase inhibitors (TKIs), but the lack of activity of immune checkpoint inhibitors (ICIs) is poorly understood. Here, we identified immunogenic ALK peptides to show that ICIs induced rejection...
CancerCancer immunotherapyNon-small-cell lung cancerTumour vaccines
10.1038/S43018-023-00591-2
ISSN:2662-1347
RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway
Xueliang Zeng•Yao Lu•Taohui Zeng•Wenyu Liu•Weicai Huang等 10 人
Communications Biology
2024
•2024/7/2
•Vol.7 No.1 p.1-13
Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, w...
Gastric cancer
10.1038/S42003-024-06477-Y
ISSN:2399-3642
SCRN1 confers hepatocellular carcinoma resistance to ferroptosis by stabilizing GPX4 via STK38-mediated phosphorylation
Yijie Tao•Shulei Yin•Kai Wei•Liyuan Zhao•Yani Cui等 24 人
Nature Cancer
2025
•2025/10/27
•00 p.1-18
Systemic therapy is the optimal choice for individuals with unresectable or advanced hepatocellular carcinoma (HCC). However its effectiveness is constrained by resistance. Ferroptosis is a unique form of regulated cell death and plays an essential role in HCC systemic therapy. Here we identified th...
CancerCell deathLysosomesPhosphorylation
10.1038/S43018-025-01061-7
ISSN:2662-1347
Mapping the temporal landscape of breast cancer using epigenetic entropy
Daniel L. Monyak•Shannon T. Holloway•Graham J. Gumbert•Lars J. Grimm•E. Shelley Hwang等 8 人
Communications Biology
2025
•2025/10/16
•Vol.8 No.1 p.1-16
Although generally unknown, the age of a newly diagnosed tumor encodes valuable etiologic and prognostic information. Here, we estimate the age of breast cancers, defined as the time from the start of growth to detection, using a measure of epigenetic entropy derived from genome-wide methylation arr...
Breast cancerCancer preventionCancer screeningPredictive markers
10.1038/S42003-025-08867-2
ISSN:2399-3642
A novel age-related gene expression signature associates with proliferation and disease progression in breast cancer
Ingebriktsen L. M.•Finne K.•Akslen L. A.•Wik E.
British Journal Of Cancer
2022
•2022/8/23
•Vol.127 No.10 p.1865-1875
Breast cancer (BC) diagnosed at ages <40 years presents with more aggressive tumour phenotypes and poorer clinical outcome compared to older BC patients. Here, we explored transcriptional BC alterations to gain a better understanding of age-related tumour biology, also subtype-stratified. We stud...
Breast cancerPrognostic markers
10.1038/S41416-022-01953-W
ISSN:0007-0920
Enterocyte-like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability
Arezo Torang•Aleksandar B. Kirov•Veerle Lammers•Kate Cameron•Valérie M. Wouters等 11 人
Nature Communications
2025
•2025/1/2
•Vol.16 No.1 p.1-16
Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4). CMS3 represents the metabolic subtype, but its wiring remains largely undefined. To identify the underlying tumorigenesis of CMS3, organoids derived from 16 genetically engineered mouse models are analyzed. Upon i...
Cancer metabolismCancer modelsColon cancer
10.1038/S41467-024-55574-3
ISSN:2041-1723
Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
Duhamel Marie•Drelich Lauranne•Wisztorski Maxence•Aboulouard Soulaimane•Gimeno Jean-Pascal等 15 人
Nature Communications
2022
•2022/11/4
•Vol.13 No.1 p.1-16
Molecular heterogeneity is a key feature of glioblastoma that impedes patient stratification and leads to large discrepancies in mean patient survival. Here, we analyze a cohort of 96 glioblastoma patients with survival ranging from a few months to over 4 years. 46 tumors are analyzed by mass spectr...
CNS cancerTumour biomarkersTumour heterogeneity
10.1038/S41467-022-34208-6
ISSN:2041-1723
MACHETE identifies interferon-encompassing chromosome 9p21.3 deletions as mediators of immune evasion and metastasis
Barriga Francisco M.•Tsanov Kaloyan M.•Ho Yu-Jui•Sohail Noor•Zhang Amy等 20 人
Nature Cancer
2022
•2022/11/7
•Vol.3 No.11 p.1367-1385
The most prominent homozygous deletions in cancer affect chromosome 9p21.3 and eliminate CDKN2A/B tumor suppressors, disabling a cell-intrinsic barrier to tumorigenesis. Half of 9p21.3 deletions, however, also encompass a type I interferon (IFN) gene cluster; the consequences of this co-deletion rem...
CancerGene targetingTumour immunology
10.1038/S43018-022-00443-5
ISSN:2662-1347
Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease
Josef Leibold•Kaloyan M. Tsanov•Corina Amor•Yu-Jui Ho•Francisco J. Sánchez-Rivera等 13 人
Nature Cancer
2024
•2024/1/4
•00 p.1-15
Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the mechanisms underlying the behavior and therapeutic response of this disease are poorly understood owing, in part, to a paucity of tracta...
CancerCancer geneticsCancer modelsTumour immunology
10.1038/S43018-023-00686-W
ISSN:2662-1347
Molecular landscape and functional characterization of centrosome amplification in ovarian cancer
Carolin M. Sauer•James A. Hall•Dominique-Laurent Couturier•Thomas Bradley•Anna M. Piskorz等 22 人
Nature Communications
2023
•2023/10/16
•Vol.14 No.1 p.1-20
High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSO...
Cancer genomicsCell divisionConfocal microscopyOvarian cancerTumour biomarkers
10.1038/S41467-023-41840-3
ISSN:2041-1723
Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors
Rom Keshet•Joo Sang Lee•Lital Adler•Muhammed Iraqi•Yarden Ariav等 30 人
Nature Cancer
2020
•2020/8/31
•Vol.1 No.9 p.894-908
Argininosuccinate synthase (ASS1) downregulation in different tumors has been shown to support cell proliferation and yet, in several common cancer subsets ASS1 expression associates with poor patient prognosis. Here we demonstrate that ASS1 expression under glucose deprivation is induced by c-MYC, ...
CancerCancer metabolism
10.1038/S43018-020-0106-7
ISSN:2662-1347
Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity
Irene Schwartz•Valentina Budroni•Mathilde Meyenberg•Zuzana Hodakova•Harald Hornegger等 15 人
Nature Communications
2026
•2026/1/19
•Vol.17 No.1 p.17230
APOBEC family members play crucial roles in antiviral restriction. However, certain APOBEC3 (A3) proteins drive harmful hypermutation in humans, contributing to cancer. The cancer-associated A3 proteins are capable of transiting from the cytosol to the nucleus, where they can cause genome mutations....
Ubiquitin ligasesUbiquitylation
10.1038/S41467-026-68420-5
ISSN:2041-1723
Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Aurel Prosz•Pranshu Sahgal•Brandon M. Huffman•Zsofia Sztupinszki•Clare X. Morris等 23 人
Npj Precision Oncology
2024
•2024/4/8
•Vol.8 No.1 p.1-14
Homologous recombination (HR) and nucleotide excision repair (NER) are the two most frequently disabled DNA repair pathways in cancer. HR-deficient breast, ovarian, pancreatic and prostate cancers respond well to platinum chemotherapy and PARP inhibitors. However, the frequency of HR deficiency in g...
Cancer genomicsHigh-throughput screening
10.1038/S41698-024-00561-6
ISSN:2397-768X
5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs
Xin Chen•Ang Li•Bao-Fa Sun•Ying Yang•Ya-Nan Han等 23 人
Nature Cell Biology
2019
•2019/7/29
•Vol.21 No.8 p.978-990
Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bla...
CancerRNA decayRNA modification
10.1038/S41556-019-0361-Y
ISSN:1465-7392
Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial
Forde Patrick M.•Anagnostou Valsamo•Sun Zhuoxin•Dahlberg Suzanne E.•Kindler Hedy L.等 27 人
Nature Medicine
2021
•2021/11/8
•00 p.1-11
Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. Here we report the results of the phase 2 PrE0505 trial ( NCT02899195 ) of the anti-PD-L1 antibody durvalumab plus platinum-pemetrexed chemotherapy for 55 pat...
Cancer genomicsCancer immunotherapyMesotheliomaPhase II trialsTumour immunology
10.1038/S41591-021-01541-0
ISSN:1546-170X
Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression
Qingsong Hu•Youqiong Ye•Li-Chuan Chan•Yajuan Li•Ke Liang等 37 人
Nature Immunology
2019
•2019/6/3
•Vol.20 No.7 p.835-851
How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative ...
Animal disease modelsAntigen processing and presentationImmune evasionImmunosurveillanceUbiquitylation
10.1038/S41590-019-0400-7
ISSN:1529-2908
Mcam stabilizes a luminal progenitor-like breast cancer cell state via Ck2 control and Src/Akt/Stat3 attenuation
Ozlen Balcioglu•Brooke L. Gates•David W. Freeman•Berhane M. Hagos•Elnaz Mirzaei Mehrabad等 7 人
Npj Breast Cancer
2024
•2024/9/14
•Vol.10 No.1 p.1-13
Cell state control is crucial for normal tissue development and cancer cell mimicry of stem/progenitor states, contributing to tumor heterogeneity, therapy resistance, and progression. Here, we demonstrate that the cell surface glycoprotein Mcam maintains the tumorigenic luminal progenitor (LP)-like...
Breast cancerCell signalling
10.1038/S41523-024-00687-7
ISSN:2374-4677
Multi-organ AI endophenotypes chart the heterogeneity of brain, eye and heart pan-disease
Aleix Boquet-Pujadas•Filippos Anagnostakis•Zhijian Yang•Ye Ella Tian•Michael R. Duggan等 14 人
Nature Mental Health
2026
•2026/1/6
•Vol.4 No.2 p.203-230
Disease heterogeneity and commonality pose critical challenges to precision medicine, as traditional approaches frequently focus on single disease entities and overlook shared mechanisms across conditions. Here, inspired by pan-cancer and multi-organ research, we introduce the concept of ‘pan-diseas...
Computational modelsGenetics research
10.1038/S44220-025-00560-X
ISSN:2731-6076
A single nucleotide variant of human PARP1 determines response to PARP inhibitors
Rivki Cashman•Alona Zilberberg•Avner Priel•Hagit Philip•Alexander Varvak等 8 人
Npj Precision Oncology
2020
•2020/4/27
•Vol.4 No.1 p.1-11
The introduction of novel cancer drugs and innovative treatments brings great hope for cancer patients, but also an urgent need to match drugs to suitable patients, since certain drugs that benefit one patient may actually harm others. The newly developed poly-ADP ribose polymerase (PARP) inhibitors...
Cancer genomicsCancer therapyPredictive markers
10.1038/S41698-020-0113-2
ISSN:2397-768X
Single cell derived mRNA signals across human kidney tumors
Matthew D. Young•Thomas J. Mitchell•Lars Custers•Thanasis Margaritis•Francisco Morales-Rodriguez等 45 人
Nature Communications
2021
•2021/6/23
•Vol.12 No.1 p.1-19
Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of norm...
Cancer genomicsTranscriptomics
10.1038/S41467-021-23949-5
ISSN:2041-1723
Detecting the mutational signature of homologous recombination deficiency in clinical samples
Doga C. Gulhan•Jake June-Koo Lee•Giorgio E. M. Melloni•Isidro Cortés-Ciriano•Peter J. Park
Nature Genetics
2019
•2019/4/15
•Vol.51 No.5 p.912-919
Mutations in BRCA1 and/or BRCA2 (BRCA1/2) are the most common indication of deficiency in the homologous recombination (HR) DNA repair pathway. However, recent genome-wide analyses have shown that the same pattern of mutations found in BRCA1/2-mutant tumors is also present in several other tumors. H...
Breast cancerCancerGynaecological cancerSoftware
10.1038/S41588-019-0390-2
ISSN:1061-4036
OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation
Bernd Schöpf•Hansi Weissensteiner•Georg Schäfer•Federica Fazzini•Pornpimol Charoentong等 17 人
Nature Communications
2020
•2020/3/20
•Vol.11 No.1 p.1-16
Rewiring of energy metabolism and adaptation of mitochondria are considered to impact on prostate cancer development and progression. Here, we report on mitochondrial respiration, DNA mutations and gene expression in paired benign/malignant human prostate tissue samples. Results reveal reduced respi...
MetabolomicsNext-generation sequencingProstate cancer
10.1038/S41467-020-15237-5
ISSN:2041-1723
Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model
Raziye Piranlioglu•EunMi Lee•Maria Ouzounova•Roni J. Bollag•Alicia H. Vinyard等 15 人
Nature Communications
2019
•2019/3/29
•Vol.10 No.1 p.1-13
Although clinically apparent metastasis is associated with late stages of cancer development, micro-metastatic dissemination may be an early event. However, the fate of these early disseminated tumor cells (DTC) remains elusive. We show that despite their capacity to disseminate into secondary organ...
Cancer microenvironmentMetastasisTumour immunology
10.1038/S41467-019-09015-1
ISSN:2041-1723
Robust and data-efficient generalization of self-supervised machine learning for diagnostic imaging
Shekoofeh Azizi•Laura Culp•Jan Freyberg•Basil Mustafa•Sebastien Baur等 36 人
Nature Biomedical Engineering
2023
•2023/6/8
•00 p.1-24
Machine-learning models for medical tasks can match or surpass the performance of clinical experts. However, in settings differing from those of the training dataset, the performance of a model can deteriorate substantially. Here we report a representation-learning strategy for machine-learning mode...
DiagnosisMedical imaging
10.1038/S41551-023-01049-7
ISSN:2157-846X
An AI-driven multi-omics framework identifies lactylation-mediated therapeutic targets to overcome drug resistance in ovarian cancer
Lijia Zhang•Qi Guo•Xue Lei•Xinyu Yin•Yun Ling等 7 人
Npj Precision Oncology
2025
•2025/12/20
0Lactylation, a recently identified histone modification derived from lactate metabolism, has emerged as a critical regulator of epigenetic reprogramming, tumor proliferation, and immune evasion. In ovarian cancer, lactate dehydrogenase A (LDHA) and other metabolic enzymes contribute to lactate accum...
CancerComputational biology and bioinformatics
10.1038/S41698-025-01150-X
ISSN:2397-768X
Ultrafast prediction of somatic structural variations by filtering out reads matched to pan-genome k-mer sets
Sohn Jang-il•Choi Min-Hak•Yi Dohun•Menon Vipin A.•Kim Yeon Jeong等 18 人
Nature Biomedical Engineering
2022
•2022/12/19
•00 p.1-14
Variant callers typically produce massive numbers of false positives for structural variations, such as cancer-relevant copy-number alterations and fusion genes resulting from genome rearrangements. Here we describe an ultrafast and accurate detector of somatic structural variations that reduces rea...
Cancer genomicsSoftware
10.1038/S41551-022-00980-5
ISSN:2157-846X
Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states
Chaligne Ronan•Gaiti Federico•Silverbush Dana•Schiffman Joshua S.•Weisman Hannah R.等 21 人
Nature Genetics
2021
•2021/9/30
•Vol.53 No.10 p.1469-1479
Single-cell RNA sequencing has revealed extensive transcriptional cell state diversity in cancer, often observed independently of genetic heterogeneity, raising the central question of how malignant cell states are encoded epigenetically. To address this, here we performed multiomics single-cell pro...
CNS cancerEpigeneticsEpigenomics
10.1038/S41588-021-00927-7
ISSN:1061-4036
The cancer-testis lncRNA lnc-CTHCC promotes hepatocellular carcinogenesis by binding hnRNP K and activating YAP1 transcription
Xia Anliang•Yuan Wenwen•Wang Qiang•Xu Jianbo•Gu Yayun等 20 人
Nature Cancer
2022
•2022/1/10
•00 p.1-16
Cancer-testis (CT) genes participate in the initiation and progression of cancer, but the role of CT-associated long non-coding RNAs (CT-lncRNAs) in hepatocellular carcinoma (HCC) is still elusive. Here, we discovered a conserved CT-lncRNA, named lnc-CTHCC, which was highly expressed in the testes a...
CancerHepatocellular carcinomaLong non-coding RNAs
10.1038/S43018-021-00315-4
ISSN:2662-1347
Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency
Liana Goehring•Sarah Keegan•Sudipta Lahiri•Wenxin Xia•Michael Kong等 13 人
Nature Communications
2024
•2024/6/3
•Vol.15 No.1 p.1-18
BRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of h...
Origin firingOrigin selectionStalled forks
10.1038/S41467-024-48286-1
ISSN:2041-1723
Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy
Ajay Subramanian•Neda Nemat-Gorgani•Timothy J. Ellis-Caleo•David G. P. van IJzendoorn•Timothy J. Sears等 25 人
Nature Cancer
2024
•2024/3/1
•00 p.1-17
Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and c...
CancerCancer microenvironmentMachine learningPredictive markersSarcoma
10.1038/S43018-024-00743-Y
ISSN:2662-1347
CD95 gene deletion may reduce clonogenic growth and invasiveness of human glioblastoma cells in a CD95 ligand-independent manner
Quijano-Rubio Clara•Silginer Manuela•Weller Michael
Cell Death Discovery
2022
•2022/7/29
•Vol.8 No.1 p.1-10
CD95 (Fas/APO-1) is a multifunctional cell surface receptor with antithetic roles. First described to mediate cell death, interactions of CD95 with its natural ligand, CD95L, have also been described to induce tumor-promoting signaling leading to proliferation, invasion and stem cell maintenance, ma...
Cancer stem cellsCell growthCell invasionCell signallingCNS cancer
10.1038/S41420-022-01133-Y
ISSN:2058-7716
An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia
Lasry Audrey•Nadorp Bettina•Fornerod Maarten•Nicolet Deedra•Wu Huiyun等 22 人
Nature Cancer
2022
•2022/12/29
•Vol.4 No.1 p.27-42
Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow immune microenvironment in adult and pediatric patients with AML. We characterize unique inflammation signatures in a subset of AML ...
Acute myeloid leukaemiaCancerCancer microenvironmentTumour immunology
10.1038/S43018-022-00480-0
ISSN:2662-1347
Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages
Toszka Bohn•Steffen Rapp•Natascha Luther•Matthias Klein•Till-Julius Bruehl等 29 人
Nature Immunology
2018
•2018/11/5
•Vol.19 No.12 p.1319-1329
Many tumors evolve sophisticated strategies to evade the immune system, and these represent major obstacles for efficient antitumor immune responses. Here we explored a molecular mechanism of metabolic communication deployed by highly glycolytic tumors for immunoevasion. In contrast to colon adenoca...
Immune evasionImmunogeneticsTumour immunology
10.1038/S41590-018-0226-8
ISSN:1529-2908
HNF4A-AS1-encoded small peptide promotes self-renewal and aggressiveness of neuroblastoma stem cells via eEF1A1-repressed SMAD4 transactivation
Song Huajie•Wang Jianqun•Wang Xiaojing•Yuan Boling•Li Dan等 15 人
Oncogene
2022
•2022/3/22
•00 p.1-15
Cancer stem cells play crucial roles in tumorigenesis and aggressiveness, while regulatory mechanisms in neuroblastoma (NB), a pediatric extracranial malignancy with highest incidence, are still unknown. Herein, a small 51-amino acid peptide (sPEP1) encoded by hepatocyte nuclear factor 4 alpha antis...
OncogenesPaediatric cancer
10.1038/S41388-022-02271-4
ISSN:0950-9232
Human endogenous retroviruses (HERVs) associated with glioblastoma risk and prognosis
Harun Mazumder•Hui-Yi Lin•Melody Baddoo•Wojciech Gałan•Diana Polania-Villanueva等 13 人
Cancer Gene Therapy
2025
•2025/5/19
•00 p.1-11
Emerging evidence suggests expression from human endogenous retrovirus (HERV) loci likely contributes to, or is a biomarker of, glioblastoma multiforme (GBM) disease progression. However, the relationship between HERV expression and GBM malignant phenotype is unclear. Applying several in silico anal...
BiomarkersCancer geneticsCNS cancer
10.1038/S41417-024-00868-3
ISSN:0929-1903
Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance
Chakravarthy Ankur•Reddin Ian•Henderson Stephen•Dong Cindy•Kirkwood Nerissa等 29 人
Nature Communications
2022
•2022/10/7
•Vol.13 No.1 p.1-17
Human papillomavirus (HPV)-associated cervical cancer is a leading cause of cancer deaths in women. Here we present an integrated multi-omic analysis of 643 cervical squamous cell carcinomas (CSCC, the most common histological variant of cervical cancer), representing patient populations from the US...
Cancer epidemiologyCancer genomicsCervical cancer
10.1038/S41467-022-33544-X
ISSN:2041-1723
A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma
Saiful E. Syafruddin•Paulo Rodrigues•Erika Vojtasova•Saroor A. Patel•M. Nazhif Zaini等 12 人
Nature Communications
2019
•2019/3/11
•Vol.10 No.1 p.1-13
Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of ...
Cancer genomicsCancer modelsRenal cell carcinoma
10.1038/S41467-019-09116-X
ISSN:2041-1723
The epigenetic regulator Mll1 is required for Wnt-driven intestinal tumorigenesis and cancer stemness
Johanna Grinat•Julian Heuberger•Ramon Oliveira Vidal•Neha Goveas•Frauke Kosel等 15 人
Nature Communications
2020
•2020/12/21
•Vol.11 No.1 p.1-15
Wnt/β-catenin signaling is crucial for intestinal carcinogenesis and the maintenance of intestinal cancer stem cells. Here we identify the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5+ stem cells and human colon carcinomas with incre...
Cancer stem cellsCell signallingGastrointestinal cancerGene regulation
10.1038/S41467-020-20222-Z
ISSN:2041-1723
The Akt/mTOR and MNK/eIF4E pathways rewire the prostate cancer translatome to secrete HGF, SPP1 and BGN and recruit suppressive myeloid cells
Daniela Brina•Adele Ponzoni•Martina Troiani•Bianca Calì•Emiliano Pasquini等 39 人
Nature Cancer
2023
•2023/7/17
•00 p.1-20
Cancer is highly infiltrated by myeloid-derived suppressor cells (MDSCs). Currently available immunotherapies do not completely eradicate MDSCs. Through a genome-wide analysis of the translatome of prostate cancers driven by different genetic alterations, we demonstrate that prostate cancer rewires ...
CancerCancer immunotherapyProstate cancerTumour immunology
10.1038/S43018-023-00594-Z
ISSN:2662-1347
Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution
Michelle Dietzen•Haoran Zhai•Olivia Lucas•Oriol Pich•Christopher Barrington等 13 人
Nature Communications
2024
•2024/7/18
•Vol.15 No.1 p.1-23
During each cell cycle, the process of DNA replication timing is tightly regulated to ensure the accurate duplication of the genome. The extent and significance of alterations in this process during malignant transformation have not been extensively explored. Here, we assess the impact of altered re...
Breast cancerCancer genomicsEvolutionary geneticsNon-small-cell lung cancer
10.1038/S41467-024-50107-4
ISSN:2041-1723
The lncRNA DAMER selectively guides m6A-dependent regulation of ATF4 and asparagine metabolism under nutrient stress in cancer
Tianyu Tao•Xianming Feng•Yi Yang•Bangdong Liu•Jiaer Liang等 26 人
Nature Cell Biology
2026
•2026/3/6
•00 p.1-15
How cancer cells couple metabolic stress sensing to orchestrate specific survival programmes is a key question. Here we show a long non-coding RNA (lncRNA)-guided epitranscriptomic mechanism orchestrating metabolic adaptation by controlling the stability of master stress regulator ATF4. Glucose or g...
Cancer metabolismLong non-coding RNAsMethylationRNA modification
10.1038/S41556-026-01905-Z
ISSN:1465-7392
Mediator subunit MED4 enforces metastatic dormancy in breast cancer
Seongyeon S. Bae•Hsiang-Hsi Ling•Jiankang Zhang•Yi Chen•Hong Chen等 11 人
Nature Cell Biology
2026
•2026/6/22
•00 p.1-16
Long-term survival in breast cancer is often limited by metastatic recurrence arising from disseminated cancer cells that persist in a dormant state. The mechanisms that enable these dormant cells to survive and subsequently reawaken remain incompletely understood. Here an unbiased genome-scale gene...
Breast cancerCancer epigeneticsExtracellular matrixMetastasis
10.1038/S41556-026-01984-Y
ISSN:1465-7392
Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma
Renáta Váraljai•Lisa Zimmer•Yahya Al-Matary•Paulien Kaptein•Lea J. Albrecht等 30 人
Nature Cancer
2023
•2023/7/31
•00 p.1-17
Recent studies suggest that BRAFV600-mutated melanomas in particular respond to dual anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibition (ICI). Here we identified an over-representation of interleukin (IL)-17–type 17 ...
CancerCancer immunotherapyMelanomaTumour immunology
10.1038/S43018-023-00610-2
ISSN:2662-1347
Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer
Lips Esther H.•Kumar Tapsi•Megalios Anargyros•Visser Lindy L.•Sheinman Michael等 50 人
Nature Genetics
2022
•2022/6/9
•Vol.54 No.6 p.850-860
Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5–10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or r...
Breast cancerDNA sequencing
10.1038/S41588-022-01082-3
ISSN:1061-4036
Nuclear localization of BRCA1-associated protein 1 is important in suppressing hepatocellular carcinoma metastasis via CTCF and NRF1/OGT axis
Xiaoyu Xie•Yu-Man Tsui•Vanilla Xin Zhang•Tiffany Ching-Yun Yu•Abdullah Husain等 13 人
Cell Death & Disease
2025
•2025/2/21
•Vol.16 No.1 p.1-11
Germline mutations of the deubiquitinase BRCA1-associated protein 1 (BAP1) lead to the “BAP1 cancer syndrome” characterized by development of cancers. However, the role of BAP1 in hepatocellular carcinoma (HCC) is unclear. We found that BAP1 was upregulated at mRNA level in human HCCs and significan...
Liver cancerOncogenesis
10.1038/S41419-025-07451-0
ISSN:2041-4889
Persister state-directed transitioning and vulnerability in melanoma
Chauvistré Heike•Shannan Batool•Daignault-Mill Sheena M.•Ju Robert J.•Picard Daniel等 36 人
Nature Communications
2022
•2022/6/1
•Vol.13 No.1 p.1-17
Melanoma is a highly plastic tumor characterized by dynamic interconversion of different cell identities depending on the biological context. Melanoma cells with high expression of the H3K4 demethylase KDM5B (JARID1B) rest in a slow-cycling, yet reversible persister state. Over time, KDM5Bhigh cells...
Mechanisms of diseaseMelanomaTumour heterogeneity
10.1038/S41467-022-30641-9
ISSN:2041-1723
pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation
Zhouxiang Liao•Lichao Yang•Xiaojing Cheng•Xuejing Huang•Qi Zhang等 14 人
Cell Death Discovery
2025
•2025/1/17
•Vol.11 No.1 p.1-13
Hepatocellular carcinoma (HCC) is a global health concern, ranking as the fourth leading cause of cancer-related deaths worldwide. However, the role of piwi-interacting RNAs (piRNAs) in HCC processes has not been extensively explored. Through small RNA sequencing, our study identified a specific piR...
Cell deathHepatocellular carcinomaPiwi RNAs
10.1038/S41420-024-02285-9
ISSN:2058-7716
Histone H3 trimethylation at lysine 36 guides m 6 A RNA modification co-transcriptionally
Huilin Huang•Hengyou Weng•Keren Zhou•Tong Wu•Boxuan Simen Zhao等 42 人
Nature
2019
•2019/3/13
•Vol.567 No.7748 p.414-419
DNA and histone modifications have notable effects on gene expression1. Being the most prevalent internal modification in mRNA, the N6-methyladenosine (m6A) mRNA modification is as an important post-transcriptional mechanism of gene regulation2–4 and has crucial roles in various normal and pathologi...
EpigeneticsRNA metabolism
10.1038/S41586-019-1016-7
ISSN:0028-0836
Deregulation of CRAD-controlled cytoskeleton initiates mucinous colorectal cancer via β-catenin
Youn-Sang Jung•Wenqi Wang•Sohee Jun•Jie Zhang•Mrinal Srivastava等 12 人
Nature Cell Biology
2018
•2018/10/22
•Vol.20 No.11 p.1303-1314
Epithelial integrity is maintained by the cytoskeleton and through cell adhesion. However, it is not yet known how a deregulated cytoskeleton is associated with cancer. We identified cancer-related regulator of actin dynamics (CRAD) as frequently mutated or transcriptionally downregulated in colorec...
CancerCytoskeletonGastrointestinal cancerTumour-suppressor proteins
10.1038/S41556-018-0215-Z
ISSN:1465-7392
Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment
Meilin Xue•Youwei Zhu•Yongsheng Jiang•Lijie Han•Minmin Shi等 23 人
Nature Communications
2023
•2023/7/31
•Vol.14 No.1 p.1-18
Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell type in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-s...
Cancer microenvironmentPancreatic cancer
10.1038/S41467-023-40314-W
ISSN:2041-1723
Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers
Li Qing-Lan•Lin Xiang•Yu Ya-Li•Chen Lin•Hu Qi-Xin等 13 人
Nature Communications
2021
•2021/11/4
•Vol.12 No.1 p.1-11
Colorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ...
Cancer epigeneticsCancer genomicsColorectal cancerEpigenomicsRNA sequencing
10.1038/S41467-021-26600-5
ISSN:2041-1723
Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
Walter Rayford•Alp Tuna Beksac•Jordan Alger•Mohammed Alshalalfa•Mohsen Ahmed等 32 人
Communications Biology
2021
•2021/6/3
•Vol.4 No.1 p.1-9
Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative ...
Cancer genomicsProstate cancerTumour immunology
10.1038/S42003-021-02140-Y
ISSN:2399-3642
Reinvigorating COTL1high NK cells via GITR signalling overcomes immune checkpoint blockade resistance in tsMHC-I-impaired tumours
Wenhua You•Chupeng Hu•Yuhan Zhang•Yedi Huang•Jianzhou Yuan等 20 人
Nature Cell Biology
2026
•2026/3/30
•00 p.1-15
Patients with impaired tumour-specific major histocompatibility complex class I (tsMHC-Iimpaired) often fail to respond to immune checkpoint blockade (ICB), presenting a major clinical challenge. However, through our multicentre investigation, we observed that a subset of patients with tsMHC-Iimpair...
Cancer immunotherapyCancer microenvironmentInnate immune cellsTumour immunology
10.1038/S41556-026-01925-9
ISSN:1465-7392
Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer
Chen Ming•Chen Runzhe•Jin Ying•Li Jun•Hu Xin等 45 人
Nature Communications
2021
•2021/11/17
•Vol.12 No.1 p.1-13
Small-cell lung cancer (SCLC) is speculated to harbor complex genomic intratumor heterogeneity (ITH) associated with high recurrence rate and suboptimal response to immunotherapy. Here, using multi-region whole exome/T cell receptor (TCR) sequencing as well as immunohistochemistry, we reveal a rathe...
Cancer genomicsSmall-cell lung cancerTumour heterogeneityTumour immunology
10.1038/S41467-021-26821-8
ISSN:2041-1723
piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer
Hong-lei Qin•Yang Han•Jian-qi Li•Qing-hua Wu•Yu-ping Du等 12 人
Npj Precision Oncology
2025
•2025/3/8
•Vol.9 No.1 p.1-15
Conventional targeted therapies primarily rely on small molecules and proteins. However, they often struggle to enter specific protein conformations, which limits their therapeutic effectiveness. In contrast, RNA therapy is emerging as a more precise and effective targeting strategy. Through differe...
Drug developmentOvarian cancer
10.1038/S41698-025-00840-W
ISSN:2397-768X
RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability
Jessica Diring•Stephane Mouilleron•Neil Q. McDonald•Richard Treisman
Nature Cell Biology
2019
•2019/6/17
•Vol.21 No.7 p.845-855
RPEL proteins, which contain the G-actin-binding RPEL motif, coordinate cytoskeletal processes with actin dynamics. We show that the ArhGAP12- and ArhGAP32-family GTPase-activating proteins (GAPs) are RPEL proteins. We determine the structure of the ArhGAP12/G-actin complex, and show that G-actin co...
ActinRHO signalling
10.1038/S41556-019-0337-Y
ISSN:1465-7392
Epigenetic reader ZMYND11 noncanonical function restricts HNRNPA1-mediated stress granule formation and oncogenic activity
Cheng Lian•Chunyi Zhang•Pan Tian•Qilong Tan•Yu Wei等 16 人
Signal Transduction And Targeted Therapy
2024
•2024/9/28
•Vol.9 No.1 p.1-22
Epigenetic readers frequently affect gene regulation, correlate with disease prognosis, and hold significant potential as therapeutic targets for cancer. Zinc finger MYND-type containing 11 (ZMYND11) is notably recognized for reading the epigenetic marker H3.3K36me3; however, its broader functions a...
Cancer geneticsOncogenes
10.1038/S41392-024-01961-7
ISSN:2059-3635
Depletion-dependent activity-based protein profiling using SWATH/DIA-MS detects serine hydrolase lipid remodeling in lung adenocarcinoma progression
Tatjana Sajic•Matej Vizovišek•Stephan Arni•Rodolfo Ciuffa•Martin Mehnert等 13 人
Nature Communications
2025
•2025/5/27
•Vol.16 No.1 p.1-24
Systematic inference of enzyme activity in human tumors is key to understanding cancer progression and resistance to therapy. However, standard protein or transcript abundances are blind to the activity status of the measured enzymes, regulated, for example, by active-site amino acid mutations or po...
Biochemical networksHydrolasesNon-small-cell lung cancer
10.1038/S41467-025-59564-X
ISSN:2041-1723
RNLS hypomethylation as a potential epigenetic marker of lung cancer metastasis: an epigenome-wide association study
Zhuangjie Guo•Jinkun Chen•Siyu Zhang•Jungang Xie•Hong Zhang等 7 人
British Journal Of Cancer
2025
•2025/12/10
•00 p.1-11
Lung cancer is highly lethal because most patients have already developed metastases at diagnosis, yet the epigenetic mechanisms driving metastasis are unclear. We performed an epigenome-wide association study on 42 lung cancer patients to identify differentially methylated positions (DMPs) in pulmo...
CancerMetastasis
10.1038/S41416-025-03283-Z
ISSN:0007-0920
Non-canonical MLL1 activity regulates centromeric phase separation and genome stability
Liang Sha•Zi Yang•Sojin An•Wentao Yang•Sungmin Kim等 13 人
Nature Cell Biology
2023
•2023/11/9
•Vol.25 No.11 p.1637-1649
Epigenetic dysregulation is a prominent feature in cancer, as exemplified by frequent mutations in chromatin regulators, including the MLL/KMT2 family of histone methyltransferases. Although MLL1/KMT2A activity on H3K4 methylation is well documented, their non-canonical activities remain mostly unex...
CentromeresGenomic instabilityHepatocellular carcinomaMitosis
10.1038/S41556-023-01270-1
ISSN:1465-7392
WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer
Karim Taouis•Sophie Vacher•Josée Guirouilh-Barbat•Jacques Camonis•Etienne Formstecher等 14 人
Cancer Gene Therapy
2023
•2023/5/29
•00 p.1-12
The tumor suppressor gene WWOX is localized in an unstable chromosomal region and its expression is decreased or absent in several types of cancer. A low expression of WWOX is associated with a poor prognosis in breast cancer (BC). It has recently been shown that WWOX contributes to genome stability...
Breast cancerMolecular biology
10.1038/S41417-023-00626-X
ISSN:0929-1903
Cytosolic pH regulates proliferation and tumour growth by promoting expression of cyclin D1
Lisa Maria Koch•Eivind Salmorin Birkeland•Stefania Battaglioni•Xiao Helle•Mayura Meerang等 11 人
Nature Metabolism
2020
•2020/10/19
•Vol.2 No.11 p.1212-1222
Enhanced growth and proliferation of cancer cells are accompanied by profound changes in cellular metabolism. These metabolic changes are also common under physiological conditions, and include increased glucose fermentation accompanied by elevated cytosolic pH (pHc)1,2. However, how these changes c...
Cancer metabolismCell-cycle exitMesotheliomaMetabolismMetabolomics
10.1038/S42255-020-00297-0
ISSN:2522-5812
Palmitoylation of GPX4 via the targetable ZDHHC8 determines ferroptosis sensitivity and antitumor immunity
Liang Zhou•Guangyu Lian•Tao Zhou•Zhe Cai•Shuai Yang等 16 人
Nature Cancer
2025
•2025/3/19
•00 p.1-18
Ferroptosis is closely linked with various pathophysiological processes, including aging, neurodegeneration, ischemia-reperfusion injury, viral infection and, notably, cancer progression; however, its post-translational regulatory mechanisms remain incompletely understood. Here we revealed a crucial...
CancerCell death and immune responsePost-translational modifications
10.1038/S43018-025-00937-Y
ISSN:2662-1347
The role of miR-92b-3p in notch signaling and monitoring of oral squamous cell carcinoma
Yudan Piao•Seung-Nam Jung•Mi Ae Lim•Sicong Zheng•Chan Oh等 16 人
Oncogene
2025
•2025/2/18
•00 p.1-12
Dysregulation of microRNAs (miRNAs) influences diverse hallmarks of cancer, including proliferative signaling, metastasis, and resistance to cell death. We explored the contribution of miR-92b-3p in oral squamous cell carcinoma (OSCC) and its potential as a monitoring biomarker. Analysis of TCGA, GE...
Oral cancerTranscription
10.1038/S41388-025-03306-2
ISSN:0950-9232
Resistance to paclitaxel is associated with a variant of the gene BCL2 in multiple tumor types
Rotem Ben-Hamo•Alona Zilberberg•Helit Cohen•Keren Bahar-Shany•Chaim Wachtel等 11 人
Npj Precision Oncology
2019
•2019/4/23
•Vol.3 No.1 p.1-11
Paclitaxel, the most commonly used form of chemotherapy, is utilized in curative protocols in different types of cancer. The response to treatment differs among patients. Biological interpretation of a mechanism to explain this personalized response is still unavailable. Since paclitaxel is known to...
Cancer genomicsHigh-throughput screeningMolecular biology
10.1038/S41698-019-0084-3
ISSN:2397-768X
Exploring the structural landscape of DNA maintenance proteins
Kenneth Bødkter Schou•Samuel Mandacaru•Muhammad Tahir•Nikola Tom•Ann-Sofie Nilsson等 9 人
Nature Communications
2024
•2024/9/5
•Vol.15 No.1 p.1-17
Evolutionary annotation of genome maintenance (GM) proteins has conventionally been established by remote relationships within protein sequence databases. However, often no significant relationship can be established. Highly sensitive approaches to attain remote homologies based on iterative profile...
Protein sequence analysesStructural biology
10.1038/S41467-024-49983-7
ISSN:2041-1723
Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer via extracellular vesicle transfer of RNA
Ziming Chen•Yifan Zhou•Chunling Xue•Lingxing Zeng•Shuang Deng等 23 人
Nature Cell Biology
2025
•2025/5/26
•00 p.1-13
The pathological role and mechanism of psychological stress in cancer progression are little known. Here we show in a mouse model that psychological stress drives pancreatic ductal adenocarcinoma (PDAC) progression by stimulating tumour nerve innervation. We demonstrate that nociception and other st...
Cancer microenvironmentPancreatic cancerRNA modification
10.1038/S41556-025-01667-0
ISSN:1465-7392
Tumor-specific cholinergic CD4+ T lymphocytes guide immunosurveillance of hepatocellular carcinoma
Chunxing Zheng•Bryan E. Snow•Andrew J. Elia•Robert Nechanitzky•Carmen Dominguez-Brauer等 21 人
Nature Cancer
2023
•2023/8/28
•00 p.1-18
Cholinergic nerves are involved in tumor progression and dissemination. In contrast to other visceral tissues, cholinergic innervation in the hepatic parenchyma is poorly detected. It remains unclear whether there is any form of cholinergic regulation of liver cancer. Here, we show that cholinergic ...
CancerHepatocellular carcinomaImmunosurveillanceTumour immunology
10.1038/S43018-023-00624-W
ISSN:2662-1347
Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers
Rachel Joyce•Rosa Pascual•Luuk Heitink•Bianca D. Capaldo•François Vaillant等 21 人
Nature Cell Biology
2024
•2024/1/12
•Vol.26 No.1 p.138-152
Inheritance of a BRCA2 pathogenic variant conveys a substantial life-time risk of breast cancer. Identification of the cell(s)-of-origin of BRCA2-mutant breast cancer and targetable perturbations that contribute to transformation remains an unmet need for these individuals who frequently undergo pro...
Breast cancerCancer stem cellsTOR signalling
10.1038/S41556-023-01315-5
ISSN:1465-7392
Systemic IFN-I combined with topical TLR7/8 agonists promotes distant tumor suppression by c-Jun-dependent IL-12 expression in dendritic cells
Martina Sanlorenzo•Philipp Novoszel•Igor Vujic•Tommaso Gastaldi•Martina Hammer等 14 人
Nature Cancer
2025
•2025/1/23
•Vol.6 No.1 p.175-193
Dendritic cell (DC) activation by pattern recognition receptors like Toll-like-receptors (TLRs) is crucial for cancer immunotherapies. Here, we demonstrate the effectiveness of the TLR7/8 agonist imiquimod (IMQ) in treating both local tumors and distant metastases. Administered orally, IMQ activates...
CancerCancer immunotherapyMelanomaToll-like receptors
10.1038/S43018-024-00889-9
ISSN:2662-1347
Derivation of prognostic contextual histopathological features from whole-slide images of tumours via graph deep learning
Lee Yongju•Park Jeong Hwan•Oh Sohee•Shin Kyoungseob•Sun Jiyu等 11 人
Nature Biomedical Engineering
2022
•2022/8/18
•00 p.1-15
Methods of computational pathology applied to the analysis of whole-slide images (WSIs) do not typically consider histopathological features from the tumour microenvironment. Here, we show that a graph deep neural network that considers such contextual features in gigapixel-sized WSIs in a semi-supe...
Image processingMachine learningPrognostic markersRenal cell carcinoma
10.1038/S41551-022-00923-0
ISSN:2157-846X
TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
Gibson Shayin V.•Tomas Bort Elena•Rodríguez-Fernández Lucía•Allen Michael D.•Gomm Jennifer J.等 15 人
Npj Breast Cancer
2023
•2023/3/2
•Vol.9 No.1 p.1-15
Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Virtually all women with DCIS are treated, despite evidence suggesting up to half would remain with stable, non-threatening, disease. Overtreatment thus presents a pressing issue in DCIS management. To understand ...
Breast cancerExtracellular matrix
10.1038/S41523-023-00513-6
ISSN:2374-4677
METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumourigenesis
Wei Xueju•Huo Yue•Pi Jingnan•Gao Yufeng•Rao Shuan等 25 人
Nature Cell Biology
2022
•2022/8/4
•Vol.24 No.8 p.1278-1290
METTL3 encodes the predominant catalytic enzyme to promote m6A methylation in nucleus. Recently, accumulating evidence has shown the expression of METTL3 in cytoplasm, but its function is not fully understood. Here we demonstrated an m6A-independent mechanism for METTL3 to promote tumour progression...
Cancer epigeneticsGastric cancerOncogenesRNA modification
10.1038/S41556-022-00968-Y
ISSN:1465-7392
LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy
Yanke Chen•Ting Jiang•Hongyi Zhang•Xingchun Gou•Cong Han等 21 人
Nature Cell Biology
2020
•2020/10/1
•Vol.22 No.10 p.1276-1285
Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation...
Breast cancerDNA damage and repairMetastasisRadiotherapy
10.1038/S41556-020-00586-6
ISSN:1465-7392
Hotspot DNMT3A mutations in clonal hematopoiesis and acute myeloid leukemia sensitize cells to azacytidine via viral mimicry response
Marina Scheller•Anne Kathrin Ludwig•Stefanie Göllner•Christian Rohde•Stephen Krämer等 29 人
Nature Cancer
2021
•2021/5/25
•Vol.2 No.5 p.527-544
Somatic mutations in DNA methyltransferase 3A (DNMT3A) are among the most frequent alterations in clonal hematopoiesis (CH) and acute myeloid leukemia (AML), with a hotspot in exon 23 at arginine 882 (DNMT3AR882). Here, we demonstrate that DNMT3AR882H-dependent CH and AML cells are specifically susc...
Acute myeloid leukaemiaCancerHaematological diseasesTranslational research
10.1038/S43018-021-00213-9
ISSN:2662-1347
Insights from pharmacovigilance databases, clinical cohorts and preclinical models into VEGF(R) inhibitor-induced arthritis in cancer
Lan Xu•Anqi Lin•Zhengrui Li•Junyi Shen•Hao Chi等 11 人
Communications Medicine
2025
•2025/11/18
•Vol.5 No.1 p.4780
VEGF and VEGFR inhibitors are key in targeted therapy for various malignancies, but arthritis-related side effects are poorly understood. This study investigates the incidence, risk factors, and molecular mechanisms of VEGF(R) inhibitor-induced arthritis. Statistical analyses of VEGF(R) inhibitor-re...
Cancer therapyMolecular biology
10.1038/S43856-025-01169-Y
ISSN:2730-664X
Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44
Amy L. Cummings•Jaklin Gukasyan•Henry Y. Lu•Tristan Grogan•Gemalene Sunga等 21 人
Nature Cancer
2020
•2020/11/16
•Vol.1 No.12 p.1167-1175
Human leukocyte antigen (HLA)-B has been recognized as a major determinant of discrepancies in disease outcomes, and recent evidence indicates a role in immune checkpoint blockade (ICB) efficacy. The B44 supertype, which features an electropositive binding pocket that preferentially displays peptide...
CancerCancer genomicsNon-small-cell lung cancerTumour immunology
10.1038/S43018-020-00140-1
ISSN:2662-1347
TIAToolbox as an end-to-end library for advanced tissue image analytics
Pocock Johnathan•Graham Simon•Vu Quoc Dang•Jahanifar Mostafa•Deshpande Srijay等 14 人
Communications Medicine
2022
•2022/9/24
•Vol.2 No.1 p.1-14
Computational pathology has seen rapid growth in recent years, driven by advanced deep-learning algorithms. Due to the sheer size and complexity of multi-gigapixel whole-slide images, to the best of our knowledge, there is no open-source software library providing a generic end-to-end API for pathol...
Cancer imagingComputational biology and bioinformatics
10.1038/S43856-022-00186-5
ISSN:2730-664X
PCBP1 binding to single-stranded poly-cytosine motifs enhances cGAS sensing and impairs breast cancer development
Cécile Fréreux•Joseph A. Q. Karam•Breege V. Howley•Bryan Granger•Paramita Chakraborty等 11 人
Communications Biology
2026
•2026/1/7
•Vol.9 No.1 p.1790
The cGAS-STING pathway plays a central role in controlling tumor progression through nucleic acid sensing and type I Interferon production. Here, we identify Poly(rC) Binding Protein 1 as a tumor suppressor that amplifies cGAS-STING signaling in breast cancer. Using patient datasets and a transgenic...
Breast cancerCell signallingDNATumour-suppressor proteins
10.1038/S42003-025-09456-Z
ISSN:2399-3642
Tumor cell-adipocyte gap junctions activate lipolysis and contribute to breast tumorigenesis
Jeremy Williams•Roman Camarda•Serghei Malkov•Lisa J. Zimmerman•Suzanne Manning等 33 人
Nature Communications
2025
•2025/8/20
•Vol.16 No.1 p.1-17
A pro-tumorigenic role for adipocytes has been identified in breast cancer, and reliance on fatty acid catabolism found in aggressive tumors. The molecular mechanisms by which tumor cells coopt neighboring adipocytes, however, remain incompletely understood. Here, we describe a direct interaction li...
Breast cancerCancer metabolism
10.1038/S41467-025-62486-3
ISSN:2041-1723
Loss of Ambra1 promotes melanoma growth and invasion
Luca Di Leo•Valérie Bodemeyer•Francesca M. Bosisio•Giuseppina Claps•Marco Carretta等 23 人
Nature Communications
2021
•2021/5/5
•Vol.12 No.1 p.1-17
Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecu...
Cell invasionFocal adhesionMelanoma
10.1038/S41467-021-22772-2
ISSN:2041-1723
Endocytic protein intersectin1-S shuttles into nucleus to suppress the DNA replication in breast cancer
Zhang Huikun•Guo Zhifang•Liu Xiaoli•Zhao Yawen•Chen Yongzi等 9 人
Cell Death & Disease
2021
•2021/10/8
•Vol.12 No.10 p.1-17
Breast cancer is the most common type of cancer worldwide. However, the well-known molecular biomarkers are not enough to meet the needs of precision medicine. In search for novel targets in this regard, we reported ITSN1 (intersectin1) as one of the candidates through mRNA microarray analysis. In t...
CancerCell biology
10.1038/S41419-021-04218-1
ISSN:2041-4889
Machine learning analysis of gene expression reveals TP53 Mutant-like AML with wild type TP53 and poor prognosis
Yoonkyu Lee•Linda B. Baughn•Chad L. Myers•Zohar Sachs
Blood Cancer Journal
2024
•2024/5/14
•Vol.14 No.1 p.1-6
Acute myeloid leukaemia
10.1038/S41408-024-01061-3
ISSN:2044-5385
A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma
Yingying Zhao•Hongmei Yu•Jiajun Li•Jiali Qian•Miao Li等 19 人
Nature Communications
2025
•2025/2/18
•Vol.16 No.1 p.1-26
Apart from the classic features, it is almost unknown whether there exist other new pathological features during pre-metastatic niche formation in hepatocellular carcinoma (HCC). Our previous works have highlighted the contribution of increased matrix stiffness to lung pre-metastatic niche formation...
Cancer microenvironmentLiver
10.1038/S41467-025-56878-8
ISSN:2041-1723
Computational image and molecular analysis reveal unique prognostic features of immune architecture in African Versus European American women with endometrial cancer
Sepideh Azarianpour•Sirvan Khalighi•Arpit Aggarwal•Vidya Sankar Viswanathan•Pingfu Fu等 7 人
Npj Precision Oncology
2025
•2025/6/23
•Vol.9 No.1 p.1-14
Endometrial cancer (EC) disproportionately affects African American (AA) women in terms of progression and death. In our study, we sought to employ computerized image and bioinformatic analysis to tease out morphologic and molecular differences in EC between AA and European-American (EA) populations...
BiomarkersCancerMathematics and computingOncologyRisk factors
10.1038/S41698-025-00972-Z
ISSN:2397-768X
HIF-1 Interacts with TRIM28 and DNA-PK to release paused RNA polymerase II and activate target gene transcription in response to hypoxia
Yang Yongkang•Lu Haiquan•Chen Chelsey•Lyu Yajing•Cole Robert N.等 6 人
Nature Communications
2022
•2022/1/14
•Vol.13 No.1 p.1-16
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that acts as a regulator of oxygen (O2) homeostasis in metazoan species by binding to hypoxia response elements (HREs) and activating the transcription of hundreds of genes in response to reduced O2 availability. RNA polymerase II (Pol II)...
Breast cancerCancer genetics
10.1038/S41467-021-27944-8
ISSN:2041-1723
Genetic fusions favor tumorigenesis through degron loss in oncogenes
Liu Jing•Tokheim Collin•Lee Jonathan D.•Gan Wenjian•North Brian J.等 8 人
Nature Communications
2021
•2021/11/18
•Vol.12 No.1 p.1-15
Chromosomal rearrangements can generate genetic fusions composed of two distinct gene sequences, many of which have been implicated in tumorigenesis and progression. Our study proposes a model whereby oncogenic gene fusions frequently alter the protein stability of the resulting fusion products, via...
Cancer geneticsCancer genomicsOncogenesUbiquitin ligasesUbiquitylation
10.1038/S41467-021-26871-Y
ISSN:2041-1723
Systemic rewiring of dendritic cells by melanoma-secreted midkine impairs immune surveillance and response to immune checkpoint blockade
Xavier Catena•Marta Contreras-Alcalde•Naiara Juan-Larrea•Daniela Cerezo-Wallis•Tonantzin G. Calvo等 18 人
Nature Cancer
2025
•2025/3/28
•00 p.1-20
Cutaneous melanomas express a high number of potential neoepitopes, yet a substantial fraction of melanomas shift into immunologically cold phenotypes. Using cellular systems, mouse models and large datasets, we identify the tumor-secreted growth factor midkine (MDK) as a multilayered inhibitor of a...
CancerCancer immunotherapyMelanomaTumour immunology
10.1038/S43018-025-00929-Y
ISSN:2662-1347
Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression
Huang De•Wang Yan•Thompson J. Will•Yin Tao•Alexander Peter B.等 15 人
Nature Cell Biology
2022
•2022/2/10
•Vol.24 No.2 p.230-241
Many cancers have an unusual dependence on glutamine. However, most previous studies have focused on the contribution of glutamine to metabolic building blocks and the energy supply. Here, we report that cancer cells with aberrant expression of glutamate decarboxylase 1 (GAD1) rewire glutamine metab...
Cancer metabolismCancer microenvironmentTumour immunology
10.1038/S41556-021-00820-9
ISSN:1465-7392
Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas
Ren Yanming•Huang Zongyao•Zhou Lingling•Xiao Peng•Song Junwei等 29 人
Nature Communications
2023
•2023/2/23
•Vol.14 No.1 p.1-19
Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA ...
Cancer genomicsCancer modelsCNS cancer
10.1038/S41467-023-36707-6
ISSN:2041-1723
Silencing growth hormone receptor inhibits estrogen receptor negative breast cancer through ATP-binding cassette sub-family G member 2
Arunkumar Arumugam•Ramadevi Subramani•Sushmita Bose Nandy•Daniel Terreros•Alok Kumar Dwivedi等 7 人
Experimental & Molecular Medicine
2019
•2019/1/7
•Vol.51 No.1 p.1-13
Growth hormone receptor (GHR) plays a vital role in breast cancer chemoresistance and metastasis but the mechanism is not fully understood. We determined if GHR could be a potential therapeutic target for estrogen receptor negative (ER−ve) breast cancer, which are highly chemoresistant and metastati...
CancerCell biologyEndocrinology
10.1038/S12276-018-0197-8
ISSN:1226-3613
Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation
Wu Chengsheng•Rakhshandehroo Taha•Wettersten Hiromi I.•Campos Alejandro•von Schalscha Tami等 13 人
Nature Cell Biology
2023
•2023/1/16
•Vol.25 No.2 p.309-322
Defining drivers of tumour initiation can provide opportunities to control cancer progression. Here we report that lysophosphatidic acid receptor 4 (LPAR4) becomes transiently upregulated on pancreatic cancer cells exposed to environmental stress or chemotherapy where it promotes stress tolerance, d...
Cancer microenvironmentCancer stem cellsTumour biomarkers
10.1038/S41556-022-01055-Y
ISSN:1465-7392
Generating crossmodal gene expression from cancer histopathology improves multimodal AI predictions
Samiran Dey•Christopher R. S. Banerji•Partha Basuchowdhuri•Sanjoy K. Saha•Deepak Parashar等 6 人
Nature Communications
2025
•2025/12/31
0Emerging research has highlighted that artificial intelligence-based multimodal fusion of digital pathology and transcriptomic features can improve cancer diagnosis (grading/subtyping) and prognosis (survival risk) prediction. However, such direct fusion is impractical in clinical settings, where hi...
Cancer genomicsCancer imagingComputational scienceMachine learningPathology
10.1038/S41467-025-66961-9
ISSN:2041-1723
Detection of pre-transition phases during biological development using single-sample network entropy (SNE)
Chengmu She•Zhirui Tang•Yuan Tao•Jiayuan Zhong•Zhengrong Liu等 6 人
Npj Systems Biology And Applications
2025
•2025/11/22
0Complex biological systems often undergo a pre-transition phase prior to the onset of catastrophic event, during which a sharp and essential shift occurs. There is a pressing need to develop a swift and effective method for identifying such pre-transition phase or critical state, facilitating the ti...
Computational biology and bioinformaticsDevelopmental biology
10.1038/S41540-025-00623-W
ISSN:2056-7189
Human-interpretable image features derived from densely mapped cancer pathology slides predict diverse molecular phenotypes
James A. Diao•Jason K. Wang•Wan Fung Chui•Victoria Mountain•Sai Chowdary Gullapally等 22 人
Nature Communications
2021
•2021/3/12
•Vol.12 No.1 p.1-15
Computational methods have made substantial progress in improving the accuracy and throughput of pathology workflows for diagnostic, prognostic, and genomic prediction. Still, lack of interpretability remains a significant barrier to clinical integration. We present an approach for predicting clinic...
Cancer imagingMachine learningPredictive markers
10.1038/S41467-021-21896-9
ISSN:2041-1723
Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo
L. Francisco Lorenzo-Martín•Tania Hübscher•Amber D. Bowler•Nicolas Broguiere•Jakob Langer等 9 人
Nature
2024
•2024/4/24
•00 p.1-8
Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of both tumour and microenvironmental structures1–3. This has enabled better modelling of low-complexity cancer cell behaviours that occur over relatively sho...
Cancer modelsGastrointestinal cancerLab-on-a-chipTissue engineering
10.1038/S41586-024-07330-2
ISSN:0028-0836
Generalisation of automatic tumour segmentation in histopathological whole-slide images across multiple cancer types
Ole-Johan Skrede•Manohar Pradhan•Maria Xepapadakis Isaksen•Tarjei Sveinsgjerd Hveem•Ljiljana Vlatkovic等 23 人
Npj Precision Oncology
2026
•2026/2/4
•Vol.10 No.1 p.1070
Deep learning is expected to aid pathologists in tasks such as tumour segmentation. We developed a general tumour segmentation model for histopathological images and examined its performance in different cancer types. The model was developed using over 20,000 whole-slide images from over 4000 patien...
CancerComputational biology and bioinformaticsOncology
10.1038/S41698-026-01311-6
ISSN:2397-768X
FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation
Warrick Joshua I.•Hu Wenhuo•Yamashita Hironobu•Walter Vonn•Shuman Lauren等 51 人
Nature Communications
2022
•2022/11/2
•Vol.13 No.1 p.1-17
Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic h...
Bladder cancerCancer genomics
10.1038/S41467-022-34251-3
ISSN:2041-1723
A software pipeline for medical information extraction with large language models, open source and suitable for oncology
Isabella Catharina Wiest•Fabian Wolf•Marie-Elisabeth Leßmann•Marko van Treeck•Dyke Ferber等 11 人
Npj Precision Oncology
2025
•2025/9/17
•Vol.9 No.1 p.1-12
In medical oncology, text data, such as clinical letters or procedure reports, is stored in an unstructured way, making quantitative analysis difficult. Manual review or structured information retrieval is time-consuming and costly, whereas Large Language Models (LLMs) offer new possibilities in nat...
CancerTranslational research
10.1038/S41698-025-01103-4
ISSN:2397-768X
METTL16 antagonizes MRE11-mediated DNA end resection and confers synthetic lethality to PARP inhibition in pancreatic ductal adenocarcinoma
Zeng Xiangyu•Zhao Fei•Cui Gaofeng•Zhang Yong•Deshpande Rajashree A.等 32 人
Nature Cancer
2022
•2022/9/22
•Vol.3 No.9 p.1088-1104
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Characterization of genetic alterations will improve our understanding and therapies for this disease. Here, we report that PDAC with elevated expression of METTL16, one of the ‘writers’ of RNA N6-methyladenosine modification...
CancerDouble-strand DNA breaksHomologous recombinationTargeted therapies
10.1038/S43018-022-00429-3
ISSN:2662-1347
Uncovering structural themes across cilia microtubule inner proteins with implications for human cilia function
Jens S. Andersen•Aaran Vijayakumaran•Christopher Godbehere•Esben Lorentzen•Vito Mennella等 6 人
Nature Communications
2024
•2024/3/27
•Vol.15 No.1 p.1-17
Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins (MIPs). To address the outstanding question of how...
CiliaComputational biology and bioinformaticsMicrotubulesProtein structure predictions
10.1038/S41467-024-46737-3
ISSN:2041-1723
Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis
Garcia-Recio Susana•Hinoue Toshinori•Wheeler Gregory L.•Kelly Benjamin J.•Garrido-Castro Ana C.等 57 人
Nature Cancer
2022
•2022/12/30
•Vol.4 No.1 p.128-147
The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and g...
Breast cancerCancerCancer epigeneticsCancer genomics
10.1038/S43018-022-00491-X
ISSN:2662-1347
High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma
Ping Feng•Ying Wang•Na Liu•Yanming Chen•Yujun Hu等 13 人
Cell Death & Differentiation
2024
•2024/4/8
•00 p.1-14
Protein phosphatase 1 catalytic subunit gamma (PPP1CC) promotes DNA repair and tumor development and progression, however, its underlying mechanisms remain unclear. This study investigated the molecular mechanism of PPP1CC’s involvement in DNA repair and the potential clinical implications. High exp...
Oncogenes
10.1038/S41418-024-01287-5
ISSN:1350-9047
Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers
Shicai Fan•Jianxiong Tang•Nan Li•Ying Zhao•Rizi Ai等 9 人
Npj Genomic Medicine
2019
•2019/2/1
•Vol.4 No.1 p.1-11
The integration of genomic and DNA methylation data has been demonstrated as a powerful strategy in understanding cancer mechanisms and identifying therapeutic targets. The TCGA consortium has mapped DNA methylation in thousands of cancer samples using Illumina Infinium Human Methylation 450 K BeadC...
CancerComputational biology and bioinformatics
10.1038/S41525-019-0077-8
ISSN:2056-7944
Caveolin-1-mediated sphingolipid oncometabolism underlies a metabolic vulnerability of prostate cancer
Jody Vykoukal•Johannes F. Fahrmann•Justin R. Gregg•Zhe Tang•Spyridon Basourakos等 19 人
Nature Communications
2020
•2020/8/27
•Vol.11 No.1 p.1-16
Plasma and tumor caveolin-1 (Cav-1) are linked with disease progression in prostate cancer. Here we report that metabolomic profiling of longitudinal plasmas from a prospective cohort of 491 active surveillance (AS) participants indicates prominent elevations in plasma sphingolipids in AS progressor...
BiochemistryCancerCell biology
10.1038/S41467-020-17645-Z
ISSN:2041-1723
Computational pathology identifies immune-mediated collagen disruption to predict clinical outcomes in gynecologic malignancies
Arpit Aggarwal•Sirvan Khalighi•Deepak Babu•Haojia Li•Sepideh Azarianpour-Esfahani等 14 人
Communications Medicine
2024
•2024/1/3
•Vol.4 No.1 p.1-12
The role of immune cells in collagen degradation within the tumor microenvironment (TME) is unclear. Immune cells, particularly tumor-infiltrating lymphocytes (TILs), are known to alter the extracellular matrix, affecting cancer progression and patient survival. However, the quantitative evaluation ...
Cancer imagingCancer microenvironmentGynaecological cancerPrognostic markers
10.1038/S43856-023-00428-0
ISSN:2730-664X
METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis
Su Rui•Dong Lei•Li Yangchan•Gao Min•He P. Cody等 32 人
Nature Cell Biology
2022
•2022/2/10
•Vol.24 No.2 p.205-216
METTL16 has recently been identified as an RNA methyltransferase responsible for the deposition of N6-methyladenosine (m6A) in a few transcripts. Whether METTL16 methylates a large set of transcripts, similar to METTL3 and METTL14, remains unclear. Here we show that METTL16 exerts both methyltransfe...
CancerRNA modificationTranslation
10.1038/S41556-021-00835-2
ISSN:1465-7392
EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis
Wang Jun•Yu Xufen•Gong Weida•Liu Xijuan•Park Kwang-Su等 17 人
Nature Cell Biology
2022
•2022/2/24
•00 p.1-16
Canonically, EZH2 serves as the catalytic subunit of PRC2, which mediates H3K27me3 deposition and transcriptional repression. Here, we report that in acute leukaemias, EZH2 has additional noncanonical functions by binding cMyc at non-PRC2 targets and uses a hidden transactivation domain (TAD) for (c...
CancerCancer epigeneticsDrug developmentTargeted therapies
10.1038/S41556-022-00850-X
ISSN:1465-7392