Oncogene最新文献

{"title":"Correction: Hypermethylation of 14-3-3 σ (stratifin) is an early event in breast cancer","authors":"Christopher B. Umbricht, Ella Evron, Edward Gabrielson, Anne T. Ferguson, Jeffrey Marks, Saraswati Sukumar","doi":"10.1038/s41388-025-03555-1","DOIUrl":"10.1038/s41388-025-03555-1","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 38","pages":"3640-3640"},"PeriodicalIF":7.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03555-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ECD, a novel androgen receptor target promotes prostate cancer tumorigenesis by regulating glycolysis","authors":"Mohsin Raza, Asher Rajkumar Rajan, Benjamin B. Kennedy, Timothy E. Reznicek, Farshid Oruji, Sameer Mirza, M. Jordan Rowley, Carsten Stephan, Glen Kristiansen, Kaustubh Datta, Bhopal C. Mohapatra, Hamid Band, Vimla Band","doi":"10.1038/s41388-025-03559-x","DOIUrl":"10.1038/s41388-025-03559-x","url":null,"abstract":"Androgen receptor (AR)-mediated signaling is essential for PC tumorigenesis. In the TCGA database we observed a positive correlation between ECD and AR expression. Consistently, Dihydrotestosterone (DHT) treatment of PC cell lines increased ECD mRNA and protein levels, and AR knockdown (KD) reduced ECD expression. Bioinformatic analysis predicted three consensus androgen response elements in the ECD promoter, and DHT treatment increased AR occupancy at the ECD promoter, and enhanced ECD promoter activity. Enzalutamide treatment decreased ECD levels, and ECD knockout (KO) in PC cells reduced oncogenic traits, suggesting a functional role of ECD to maintain PC oncogenesis. ECD mRNA and protein are overexpressed in PC patient tissues, and its overexpression predicts shorter survival. Overexpression of ECD in PC cell lines enhanced the oncogenic traits in vitro and developed faster and larger highly proliferative xenograft tumors. RNA-seq analysis of mouse tumors revealed an increase in mRNA levels of several glycolytic genes. ECD associates with mRNA of key glycolytic genes and is required for their stability, consistent with our recent demonstration of ECD is an RNA binding protein. Higher glucose uptake and glycolysis was seen upon ECD overexpression in PC cells. Together, we demonstrate the role of a novel AR target gene ECD in PC tumorigenesis.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 42","pages":"4058-4074"},"PeriodicalIF":7.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03559-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM29 promotes bladder cancer invasion by regulating the intermediate filament network and focal adhesion","authors":"Yin Wang, Nicole A. Jerome, Alan J. Kelleher, Marian L. Henderson, Mark L. Day, Pierre A. Coulombe, Phillip L. Palmbos","doi":"10.1038/s41388-025-03557-z","DOIUrl":"10.1038/s41388-025-03557-z","url":null,"abstract":"Bladder cancer is a common malignancy whose lethality is determined by invasive potential. We have previously shown that TRIM29, also known as ATDC, is transcriptionally regulated by TP63 in basal bladder cancers where it promotes invasive progression and metastasis, but the molecular events which promote invasion and metastasis downstream of TRIM29 remained poorly understood. Here we identify stimulation of bladder cancer migration as the specific role of TRIM29 during invasion. We show that TRIM29 physically interacts with K14+ intermediate filaments which, in turn, regulates focal adhesion stability. Further, we find that both K14 and the focal adhesion protein, ZYX are required for bladder cancer migration and invasion. Taken together, these results establish a role for TRIM29 in the regulation of cytoskeleton and focal adhesions during invasion and identify a pathway with therapeutic potential.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 42","pages":"4047-4057"},"PeriodicalIF":7.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03557-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated control of cancer stemness by σ1 receptor in advanced prostate cancer","authors":"Gianluca Civenni, Giada Sandrini, Jessica Merulla, Carola Musumeci, Elisa Federici, Arianna Vallegra, Aleksandra Kokanovic, Simone Mosole, Dheeraj Shinde, Elisa Sorrenti, Alyssa J. J. Paganoni, Martina Marchetti, Riccardo Valzelli, Domenico Albino, Matteo Pecoraro, Andrea Rinaldi, Marco Bolis, Roger Geiger, Tobias Winge, Catharina Holtschulte, Erik Laurini, Sabrina Pricl, Giuseppina M. Carbone, Bernhard Wünsch, Carlo V. Catapano","doi":"10.1038/s41388-025-03541-7","DOIUrl":"10.1038/s41388-025-03541-7","url":null,"abstract":"Cancer stem cells (CSCs) are pervasively present in human cancers and have a fundamental role in treatment failure and disease recurrence. Identifying critical elements that sustain the CSC phenotype may lead to novel strategies for cancer treatment. Here, we provide evidence of an essential link between the σ1 receptor (σ1R), a ligand-regulated chaperone protein residing preferentially at the endoplasmic reticulum-mitochondria contact sites, and CSCs in castration-resistant prostate cancers (CRPCs). Integrating functional assays in multiple preclinical models with transcriptomic and proteomic data, we found that σ1R controls CSC self-renewal capacity and tumorigenic proficiency by coordinating mitochondrial dynamics and mitochondrial-nuclear signaling. Inhibiting σ1R with synthetic antagonists and RNA interference led to the progressive exhaustion and loss of tumorigenicity of the CSC progeny. Mechanistically, interfering with σ1R function disrupted mitochondria homeostasis and triggered β-catenin degradation. Examining clinical CRPC samples, we found a tight correlation between σ1R and mitochondrial gene expression. Furthermore, σ1R and β-catenin protein levels were highly correlated in prostate tumors with significant upregulation in metastatic CRPCs, sustaining a role of the σ1R-mitochondria-β-catenin axis in disease progression. This σ1R-centered axis is essential for preserving the self-renewal and tumorigenic capability of CSCs and represents a critical vulnerability exploitable for discovering novel CSC-directed therapies.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 42","pages":"4032-4046"},"PeriodicalIF":7.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03541-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NeuroD1 drives a KAT2A-FDFT1 signaling axis to promote cholesterol biosynthesis and hepatocellular carcinoma progression via histone H3K27 acetylation","authors":"Zheng Wu, Wei Duan, Ying Xiong, Jingyi Liu, Xinpeng Wen, Fuqiang Zhao, Debing Xiang, Jian Wang, Vivi Kasim, Shourong Wu","doi":"10.1038/s41388-025-03534-6","DOIUrl":"10.1038/s41388-025-03534-6","url":null,"abstract":"Abnormal lipid metabolism is one of the hallmarks of cancer. Lipid metabolic reprogramming, which has been observed in various tumors, could participate in tumor occurrence, invasion, and metastasis of tumors by regulating various carcinogenic signaling pathways. However, the molecular mechanism that regulates tumor cell lipid metabolic reprogramming has not been fully elucidated. Recent studies revealed that neurogenic differentiation factor 1 (NeuroD1) is upregulated in a variety of tumor cells, and is associated with tumorigenesis and poor prognosis. However, its role in tumor cell lipid metabolism remains unclear. Here, we found that NeuroD1 is highly expressed in hepatocellular carcinoma (HCC) cells and is associated with tumor cell cholesterol biosynthesis. We found that NeuroD1 enhances HCC cell cholesterol biosynthesis, leading to an increase in their viability. Mechanistically, NeuroD1 binds to the promoter of farnesyl diphosphate farnesyl transferase 1 (FDFT1), thereby activating its transcription activity. Furthermore, NeuroD1 can promote FDFT1 transcription through lysine acetyltransferase 2A-mediated H3K27 acetylation. Subsequently, we found that NeuroD1/FDFT1-mediated cholesterol biosynthesis is critical to the tumorigenic potential of HCC cells. These findings not only identify NeuroD1 as a regulator of lipid metabolism in tumor cells, but also reveal a novel molecular mechanism underlying its carcinogenic function.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 42","pages":"4017-4031"},"PeriodicalIF":7.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTUB1 antagonizes TRIM21 to induce deubiquitination of SPHK1 and promote the progression of hepatocellular carcinoma","authors":"Chen Sun, Shuang Cai, Jun Yang, Mingyang Du, Qi Pan, Yutao Wang, Wei Sun, Ming Bai, Hongyuan Liang","doi":"10.1038/s41388-025-03556-0","DOIUrl":"10.1038/s41388-025-03556-0","url":null,"abstract":"SPHK1 is critical for maintaining cellular lipid balance. Aberrant expression of SPHK1 aggravates malignancy of tumor through multiple signaling pathways. Here, we report a novel regulatory mechanism in ubiquitination of SPHK1. It is demonstrated that TRIM21 facilitates SPHK1 degradation via promoting K48-linked polyubiquitination. OTUB1 prohibits the TRIM21-induced ubiquitination of SPHK1 to maintain its high expression level. These findings define a new insight into the ubiquitination regulatory axis of SPHK1 and demonstrate that OTUB1-mediated SPHK1 stabilization facilitates proliferation and migration of HCC cells.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 41","pages":"3985-3998"},"PeriodicalIF":7.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LZTR1 is a melanoma oncogene that promotes invasion and suppresses apoptosis","authors":"Antonella Bacchiocchi, Michael Mak, Zerin Mahzabin Khan, Xiangyu Gong, Mario Sznol, Zhenkun Na, Haomiao Su, Lok Hei Chan, Qin Yan, Dejian Zhao, Ryland D. Mortlock, James Knight, Sarah A. Slavoff, Ruth Halaban","doi":"10.1038/s41388-025-03538-2","DOIUrl":"10.1038/s41388-025-03538-2","url":null,"abstract":"Leucine zipper like transcription regulator 1 (LZTR1) is amplified in acral melanomas, is required for melanocytes and melanoma cell proliferation, and it induces anchorage-independent growth, by yet unknown mechanisms. We therefore performed comprehensive studies to identify its activity in melanomas employing proximity biotinylation and co-immunoprecipitation combined with LC-MS/MS proteomics and molecular characterization. The results show that LZTR1 regulates the ubiquitin proteasome system in melanoma cells and also associates with actin-related proteins and actin cytoskeleton organization. Its downregulation suppresses the protective effect of the autophagy-initiating ULK1 and AMBRA1, regulators of normal cell survival and proliferation, and upregulates the sequestosome 1 (SQSTM1/p62), an autophagic cargo adapter which mediates selective degradation of ubiquitinated proteins. In contrast, overexpression of LZTR1 provides growth advantage under environmental stress, enhancing cell invasion, by activating ERBB3 receptor and its downstream targets PYK2 and SRC tyrosine kinases that regulate the cytoskeleton, actin organization, cell spreading, cell migration and adhesion. LZTR1 is a “safeguard” for melanoma cells under stress and its downregulation can be exploited for melanoma therapy.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 41","pages":"3974-3984"},"PeriodicalIF":7.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03538-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RBM30 recruits DOT1L to activate STAT1 transcription and drive immune evasion in hepatocellular carcinoma","authors":"Hexu Han, Chen Gong, Yue Zhang, Cuixia Liu, Yifan Wang, Dakun Zhao, Junxing Huang, Zhicheng Gong","doi":"10.1038/s41388-025-03550-6","DOIUrl":"10.1038/s41388-025-03550-6","url":null,"abstract":"Programmed death ligand 1 (PD-L1) is a protein expressed in hepatocellular carcinoma (HCC) that drives immune evasion by binding to programmed death receptor 1 (PD-1) on activated T cells. Understanding PD-L1 regulation is essential to understand the immunosuppressive microenvironment for antitumor immunity. We screened ribonucleic acid (RNA)-binding motif proteins (RBMs). RBM30 can enhance PD-L1 expression in HCC cells. In this study, we found that high RBM30 expression in tumor tissues can drive HCC tumor immune evasion and accelerate disease progression via increased PD-L1 transcription. We conducted multiple molecular and high-throughput assays to elucidate the intrinsic molecular mechanisms by which RBM30 upregulates PD-L1 expression in HCC. RBM30 binds to DNA near the transcriptional start site of STAT1 and recruits DOT1L to promote H3K79me3 enrichment, enhancing its accessibility to upregulate STAT1 transcription, consequently activating the PD-L1 transcription. This enhances PD-L1 expression to facilitate immune evasion. These findings reveal the vital role of RBM30 in HCC immune evasion.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 41","pages":"3955-3973"},"PeriodicalIF":7.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: COL5A1 promotes triple-negative breast cancer progression by activating tumor cell-macrophage crosstalk","authors":"Xi Chen, Chenao Ma, Yaming Li, Yiran Liang, Tong Chen, Dianwen Han, Dan Luo, Ning Zhang, Wenjing Zhao, Lijuan Wang, Qifeng Yang","doi":"10.1038/s41388-025-03554-2","DOIUrl":"10.1038/s41388-025-03554-2","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 37","pages":"3525-3526"},"PeriodicalIF":7.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03554-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the adaptive survival mechanisms of breast cancer dormancy","authors":"Francis M. Barnieh, Jamie Morton, Olaitan Olanrewaju, Sherif F. El-Khamisy","doi":"10.1038/s41388-025-03529-3","DOIUrl":"10.1038/s41388-025-03529-3","url":null,"abstract":"Breast cancer (BC) recurrence remains a major clinical challenge, leaving patients in perpetual uncertainty about disease relapse after primary treatment. BC dormancy, an adaptive survival state of disseminated tumour cells, is a key driver of both early and late recurrence. However, the mechanisms regulating BC dormancy remain poorly understood. Emerging evidence suggests that tumour hypoxia, extracellular matrix (ECM) remodelling, and therapy-induced stress drive dormancy by altering cellular metabolism, gene expression, and immune interactions, enabling long-term survival of dormant BC cells. With no dormancy-specific therapies currently approved, a deeper understanding of dormancy-associated survival mechanisms is crucial for identifying therapeutic targets and developing strategies to eradicate dormant BC cells, thereby preventing recurrence and improving patient outcomes. This review comprehensively examines major dormancy-inducing factors and the adaptive survival mechanisms of dormant BC cells. We also highlight critical gaps in preclinical models that hinder the translation of preclinical cancer dormancy insights into clinical applications and propose potential therapeutic strategies to prevent BC recurrence.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 40","pages":"3759-3773"},"PeriodicalIF":7.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03529-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}