Oncogene最新文献

{"title":"The coagulation and tumor system are directly linked through the proteolysis and activation of epidermal growth factor receptor by thrombin.","authors":"Tianfa Wang, Zhiyuan Shen, Liu Yang, Xiaohan Zhang, Min Yu, Sanjian Yu, Bing Zhao","doi":"10.1038/s41388-025-03296-1","DOIUrl":"https://doi.org/10.1038/s41388-025-03296-1","url":null,"abstract":"<p><p>Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer. Unfortunately, this knowledge has not yet led to any breakthrough in cancer therapy. Thrombin is the key enzyme of blood coagulation system. The identification of a direct link between thrombin and the tumor progression remains unknown. We illustrated thrombin expression in lung adenocarcinoma (LUAD) was closely related to clinicopathological features, prognosis, and chemotherapy outcome of patients via TCGA and clinical pathological analysis. Using genetic and pharmacological approaches, we showed a direct link between thrombin catalytic activity and lung cancer progression in vitro and in vivo. Furthermore, we revealed that thrombin cleaves epidermal growth factor receptor (EGFR) at a GRG motif perfectly conserved across disparate species, indicating functional importance, which results in activation of EGFR/AKT/mTOR signaling pathway. Last we found the mutual interaction between thrombin and chemotherapy resistance. Combination therapy of thrombin inhibitor and chemotherapy results in improved anti-tumor efficacy. Together, our data firstly revealed a mechanism of cancer progression and chemotherapy resistance that involves thrombin-mediated EGFR cleavage. We propose that thrombin could be a prognostic biomarker for lung cancer, blockade of thrombin is a valuable therapeutic strategy to overcome cancer's resistance to chemotherapy.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256339","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: FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis","authors":"Dan-Yun Ruan,&nbsp;Ting Li,&nbsp;Ying-Nan Wang,&nbsp;Qi Meng,&nbsp;Yang Li,&nbsp;Kai Yu,&nbsp;Min Wang,&nbsp;Jin-Fei Lin,&nbsp;Li-Zhi Luo,&nbsp;De-Shen Wang,&nbsp;Jun-Zhong Lin,&nbsp;Long Bai,&nbsp;Ze-Xian Liu,&nbsp;Qi Zhao,&nbsp;Xiang-Yuan Wu,&nbsp;Huai-Qiang Ju,&nbsp;Rui-Hua Xu","doi":"10.1038/s41388-025-03287-2","DOIUrl":"10.1038/s41388-025-03287-2","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 8","pages":"558-558"},"PeriodicalIF":6.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03287-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190189","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":"Correction: BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression","authors":"Yanjie Kong,&nbsp;Tianlong Lan,&nbsp;Luzhen Wang,&nbsp;Chen Gong,&nbsp;Wenxin Lv,&nbsp;Hailin Zhang,&nbsp;Chengang Zhou,&nbsp;Xiuyun Sun,&nbsp;Wenjing Liu,&nbsp;Haihui Huang,&nbsp;Xin Weng,&nbsp;Chang Cai,&nbsp;Wenfeng Peng,&nbsp;Meng Zhang,&nbsp;Dewei Jiang,&nbsp;Chuanyu Yang,&nbsp;Xia Liu,&nbsp;Yu Rao,&nbsp;Ceshi Chen","doi":"10.1038/s41388-024-03250-7","DOIUrl":"10.1038/s41388-024-03250-7","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 8","pages":"557-557"},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03250-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123304","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":"Alcohol-induced C/EBP β-driven VIRMA decreases oxidative stress and promotes pancreatic ductal adenocarcinoma growth and metastasis via the m6A/YTHDF2/SLC43A2 pathway.","authors":"Lei Gao, Gaoyuan Lv, Ziying Liu, Yitong Tian, Fang Han, Le Li, Gang Wang, Yuhua Zhang","doi":"10.1038/s41388-025-03283-6","DOIUrl":"https://doi.org/10.1038/s41388-025-03283-6","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) plays a role in the development of tumors. However, the specific role of VIRMA, an RNA methyltransferase, in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study shows that VIRMA expression is elevated in PDAC. Increased VIRMA levels promoted PDAC growth and spread, while reducing VIRMA expression slowed these processes. VIRMA facilitated SLC43A2 mRNA degradation through an m6A-YTHDF2 pathway. The resulting decrease in SLC43A2 reduced phenylalanine absorption and oxidative stress, further driving PDAC progression. Furthermore, alcohol increased C/EBP β expression, which bound to VIRMA's promoter, enhancing its transcription. These findings suggest a connection between alcohol consumption, m6A modifications, and phenylalanine absorption in PDAC progression, offering a new approach to combat this disease.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123303","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":"Phospho-TRIM21 orchestrates RPA2 ubiquitination switch to promote homologous recombination and tumor radio/chemo-resistance.","authors":"Jie Zhang, Bin Chen, Feng Xu, Ruru Wang, Xipeng Zhao, Zhicheng Yao, Jie Zhang, Shenglan Zhou, An Xu, Lijun Wu, Guoping Zhao","doi":"10.1038/s41388-025-03288-1","DOIUrl":"https://doi.org/10.1038/s41388-025-03288-1","url":null,"abstract":"<p><p>RPA2, a key component of the RPA complex, is essential for single-stranded DNA (ssDNA) binding and DNA repair. However, the regulation of RPA2-ssDNA interaction and the recruitment of repair proteins following DNA damage remain incompletely understood. Our study uncovers a novel mechanism by which phosphorylated TRIM21 (Phospho-TRIM21) regulates RPA2 ubiquitination, thereby modulating homologous recombination and tumor radio/chemo-resistance. In the absence of DNA damage, TRIM21 mediates K63-linked ubiquitination of RPA2, countering K6-linked ubiquitination. Upon DNA damage, ubiquitination-modified RPA2 binds ssDNA, stabilizing the DNA structure and facilitating ATRIP/ATR recruitment. ATR subsequently phosphorylates TRIM21 at Ser41, leading to the dissociation of the TRIM21-RPA2 complex and a shift in RPA2 ubiquitination from K63 to K6 linkage. This shift maintains RPA2 ubiquitination homeostasis and stabilizes the RPA2-ATRIP complex, which is crucial for efficient homologous recombination (HR) repair and enhanced tumor radio/chemo-resistance. We also demonstrate that TRIM21 is frequently upregulated in cancers, and its depletion sensitizes cancer cells to radio/chemotherapy, suggesting its potential as a therapeutic target. This study provides novel insights into TRIM21's role in the DNA damage response and its implications for cancer treatment.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123306","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: PIK3CAH1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling","authors":"H. Cheng,&nbsp;P. Liu,&nbsp;C. Ohlson,&nbsp;E. Xu,&nbsp;L. Symonds,&nbsp;A. Isabella,&nbsp;W. J. Muller,&nbsp;N. U. Lin,&nbsp;I. E. Krop,&nbsp;T. M. Roberts,&nbsp;E. P. Winer,&nbsp;C. L. Arteaga,&nbsp;J. J. Zhao","doi":"10.1038/s41388-025-03281-8","DOIUrl":"10.1038/s41388-025-03281-8","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 7","pages":"478-479"},"PeriodicalIF":6.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03281-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075179","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":"CREB1-BCL2 drives mitochondrial resilience in RAS GAP-dependent breast cancer chemoresistance.","authors":"Ki-Fong Man, Omeed Darweesh, Jinghui Hong, Alexandra Thompson, Charlotte O'Connor, Chiara Bonaldo, Mark N Melkonyan, Mo Sun, Rajnikant Patel, Leif W Ellisen, Tim Robinson, Dong Song, Siang-Boon Koh","doi":"10.1038/s41388-025-03284-5","DOIUrl":"https://doi.org/10.1038/s41388-025-03284-5","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive and heterogenous breast cancer subtype. RASAL2 is a RAS GTPase-activating protein (GAP) that has been associated with platinum resistance in TNBC, but the underlying mechanism is unknown. Here, we show that RASAL2 is enriched following neoadjuvant chemotherapy in TNBC patients. This enrichment is specific to the tumour compartment compared to adjacent normal tissues, suggesting that RASAL2 upregulation is tumour-selective. Analyses based on 2D/3D cultures and patient-derived xenograft models reveal that RASAL2 confers cross-resistance to common DNA-damaging chemotherapies other than platinum. Mechanistically, we found that apoptotic signalling is significantly downregulated upon RASAL2 expression. This feature is characterised by substantial alterations in the expression of anti-versus pro-apoptotic factors, pointing to heterogeneous mechanisms. In particular, RASAL2 upregulates BCL2 via activation of the oncogenic transcription co-factor YAP. CREB1, a YAP-interacting protein, was identified as the common transcription factor that binds to the promoter regions of RASAL2 and BCL2, driving their collective expression. A subset of RASAL2 colocalises with BCL2 subcellularly. Both proteins decorate mitochondria, where the high levels of mitochondrial RASAL2-induced BCL2 expression render the organelles refractory to apoptosis. Accordingly, mitochondrial outer membrane permeabilisation assay using live mitochondria from RASAL2-high/chemoresistant tumour cells demonstrated attenuated release of death signal, cytochrome c, when exposed to pro-apoptotic factors BAX and tBID. Similarly, these cells were more resilient towards chemotherapy-induced mitochondrial depolarisation. Together, this work reveals a previously undocumented molecular link between RAS GAP and apoptosis regulation, providing a new mechanistic framework for targeting a subset of chemorefractory tumours.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075184","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":"Editorial Expression of Concern: Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4–miR-18a pathway in cervical cancer","authors":"Peixin Dong,&nbsp;Ying Xiong,&nbsp;Jiehai Yu,&nbsp;Lin Chen,&nbsp;Tang Tao,&nbsp;Song Yi,&nbsp;Sharon J. B. Hanley,&nbsp;Junming Yue,&nbsp;Hidemichi Watari,&nbsp;Noriaki Sakuragi","doi":"10.1038/s41388-025-03285-4","DOIUrl":"10.1038/s41388-025-03285-4","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 7","pages":"480-480"},"PeriodicalIF":6.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03285-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067230","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":"Correction: Novel targeted mtLivin nanoparticles treatment for disseminated diffuse large B-cell lymphoma","authors":"Ihab Abd-Elrahman,&nbsp;Taher Nassar,&nbsp;Noha Khairi,&nbsp;Riki Perlman,&nbsp;Simon Benita,&nbsp;Dina Ben Yehuda","doi":"10.1038/s41388-025-03282-7","DOIUrl":"10.1038/s41388-025-03282-7","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 7","pages":"477-477"},"PeriodicalIF":6.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03282-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067229","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":"Correction: Loss-of-function mutations of SOX17 lead to YAP/TEAD activation-dependent malignant transformation in endometrial cancer","authors":"Mengfei Wang,&nbsp;Qin Yan,&nbsp;Yunfeng Song,&nbsp;Zhenbo Zhang,&nbsp;Xiaojun Chen,&nbsp;Kun Gao,&nbsp;Xiaoping Wan","doi":"10.1038/s41388-025-03280-9","DOIUrl":"10.1038/s41388-025-03280-9","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 7","pages":"476-476"},"PeriodicalIF":6.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03280-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053133","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}