Oncogene最新文献

{"title":"Small extracellular vesicle-miR-183-5p mediated crosstalk between tumor cells and macrophages in high-risk pancreatic neuroendocrine tumors.","authors":"Wuhu Zhang, Junfeng Xu, Dan Huang, Yi Qin, Xin Lou, Heli Gao, Zeng Ye, Fei Wang, Yan Wang, Desheng Jing, Guixiong Fan, Qifeng Zhuo, Chang Xin, Jie Chen, Xiaowu Xu, Xianjun Yu, Shunrong Ji","doi":"10.1038/s41388-025-03462-5","DOIUrl":"https://doi.org/10.1038/s41388-025-03462-5","url":null,"abstract":"<p><p>High-risk pancreatic neuroendocrine tumors (pNET) are characterized by aggressive progression and metastasis, contributing to poor clinical outcomes. This study explores molecular mechanisms underlying metastasis in high-risk pNETs and evaluates therapeutic interventions. We employed small RNA sequencing to profile miRNA signatures in tumor-derived small extracellular vesicles (sEVs) and integrated single-cell transcriptomic analysis to delineate the tumor immune microenvironment. Prognostic validation of SPP1+ macrophages was performed in clinical cohorts using multiplex immunofluorescence. Mechanistic studies utilized animal models and functional assays to elucidate the sEV-mediated crosstalk between tumor cells and macrophages. Here, we reveal that sEV-miR-183-5p from high-risk pNETs reprograms macrophages via PDCD4/PI3Kγ/AKT/mTOR signaling, inducing SPP1 overexpression and M2 polarization to promote angiogenesis and metastasis. p53 mutants were identified as upstream regulators of sEV-miR-183-5p secretion. Inhibition of SPP1 attenuated tumor progression, while elevated plasma sEV-miR-183-5p levels correlated with high-grade and advanced disease stages. Together, this study reveals a critical sEV-miRNA mediated mechanism governing tumor-macrophage communication in high-risk pNETs, offering insights into therapeutic strategies and suggesting sEV-miR-183-5p may have prognostic potential.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234708","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":"NRF2-mediated persistent adaptation of oesophageal adenocarcinoma cells to HER2 inhibition.","authors":"Wei Zhang, Jiaqing Lang, Sorayut Chattrakarn, Chun Wai Wong, Shiyang Li, Karmern Kan, Hongcai Liu, Wenchao Gu, Jingwei Zhang, Jukka Westermarck, Alan J Whitmarsh, Andrew D Sharrocks, Cathy Tournier","doi":"10.1038/s41388-025-03459-0","DOIUrl":"https://doi.org/10.1038/s41388-025-03459-0","url":null,"abstract":"<p><p>The human epidermal growth factor receptor 2 (HER2, also known as ERBB2) is a commonly over-expressed oncoprotein in oesophageal adenocarcinoma (OAC). Nonetheless, HER2-blocking agents have failed to significantly improve the outcome for OAC patients, despite achieving striking clinical success in breast cancer. To address this conundrum, we investigated how resistance progressively emerges when HER2 is targeted. We discovered that OAC cell lines that are capable of surviving in the presence of the dual HER1/HER2 tyrosine kinase inhibitor lapatinib exhibit a significant increase in the protein level of nuclear factor erythroid 2-related factor 2 (NRF2). Indeed, NRF2 knockdown enhanced the cytotoxic effect of lapatinib, while increased NRF2 expression in OAC cells reduced their sensitivity to HER inhibition. Furthermore, prolonged overexpression of NRF2 made OAC cell lines increasingly dependent on NRF2 for growth. Further analyses indicated that the activation of NRF2-mediated transcription that was associated with lapatinib-induced persistent and resistant phenotypes coincided with a subsequent increase in glutathione metabolism. Importantly, lapatinib resistant OAC xenografts become exquisitely sensitive to pharmacological inhibition of the NRF2 pathway. Together, these findings highlight a promising therapeutic strategy for treating refractory OAC by targeting the NRF2 pathway in combination with receptor tyrosine kinase inhibition.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234707","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":"SFXN1 promotes bladder cancer metastasis by restraining PINK1-dependent mitophagy.","authors":"Baochao Zhang, Guanqun Dong, Xinyue Guo, Hao Li, Wei Chen, Wenli Diao, Qun Lu, Guanghui Xu, Qing Zhang, Meng Ding, Hongqian Guo","doi":"10.1038/s41388-025-03460-7","DOIUrl":"https://doi.org/10.1038/s41388-025-03460-7","url":null,"abstract":"<p><p>Sideroflexin 1 (SFXN1), a newly identified mitochondrial serine transporter, exhibits great potential to modulate mitochondrial function and promote tumor development. However, its role in bladder cancer (BLCA) remains unclear. Our study revealed that SFXN1 was enriched in clinical BLCA tissues, and high SFXN1 expression in BLCA was positively associated with the progression and poor prognosis. Further, SFXN1 deficiency remarkably suppressed the proliferation and metastasis of BLCA cells in vitro and in vivo, indicating an oncogenic role of SFXN1 in BLCA. Additionally, our results demonstrated that SFXN1 promotes metastasis through its unknown function of restraining PINK1 (PTEN-induced kinase 1)-dependent mitophagy rather than its classical role as a mitochondrial serine transporter to mediate one-carbon metabolism. Mechanistically, SFXN1 acted as a bridge to promote PINK1 degradation by interacting with PARL (presenilin-associated rhomboid-like protein) and MPP-β (mitochondrial processing peptidase-β), leading to mitophagy arrest. Notably, when mitophagy was restrained by highly-expressed SFXN1, mitochondrial reactive oxygen species were considerably enriched, thus activating TGF-β (transforming growth factor-β)-mediated epithelial-mesenchymal transition and promoting metastasis of BLCA cells. This study highlights SFXN1 as a novel promising therapeutic target for BLCA and identifies a new mitophagic modulator to improve our understanding of an association between mitophagy and BLCA progression. Schematic diagram of the proposed mechanism by which SFXN1 promotes bladder cancer metastasis by restraining PINK1-dependent mitophagy. SFXN1 is upregulated in BLCA tissues, and promotes BLCA metastasis through its unrevealed function of restraining PINK1-dependent mitophagy rather than its classical role as a mitochondrial serine transporter to promote cell proliferation. Specifically, SFXN1 acted as an essential bridging factor to promote PINK1 degradation by interacting with PARL and MPP-β on the IMM, leading to mitophagy arrest and mtROS accumulation, thus activated TGF-β-mediated EMT and promoted BLCA metastasis (This figure was created by Figdraw).</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226114","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: Functional mitochondrial respiration is essential for glioblastoma tumour growth.","authors":"Petra Brisudova, Dana Stojanovic, Jaromir Novak, Zuzana Nahacka, Gabriela Lopes Oliveira, Ondrej Vanatko, Sarka Dvorakova, Berwini Endaya, Jaroslav Truksa, Monika Kubiskova, Alice Foltynova, Daniel Jirak, Natalia Jirat-Ziolkowska, Lukas Kucera, Karel Chalupsky, Krystof Klima, Jan Prochazka, Radislav Sedlacek, Francesco Mengarelli, Patrick Orlando, Luca Tiano, Paulo Oliveira, Carole Grasso, Michael V Berridge, Renata Zobalova, Miroslava Anderova, Jiri Neuzil","doi":"10.1038/s41388-025-03451-8","DOIUrl":"10.1038/s41388-025-03451-8","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226112","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":"Immunometabolism of regulatory T cells in cancer","authors":"Jordy Saravia,&nbsp;Hongbo Chi","doi":"10.1038/s41388-025-03458-1","DOIUrl":"10.1038/s41388-025-03458-1","url":null,"abstract":"Regulatory T (Treg) cells play critical roles in maintaining immune tolerance and tissue homeostasis, but impede anti-tumor immunity. Recent work has established how Treg cells metabolically adapt within the tumor microenvironment (TME), and these adaptations frequently provide a functional advantage over effector T cells. Further, enhanced Treg cell function in the TME may contribute to the limited efficacy of current immunotherapies, especially immune checkpoint blockade (ICB). Here, we review recent progress in understanding mechanisms of Treg cell heterogeneity and function in tumors, with a particular focus on cellular metabolism as an underlying factor by which Treg cells are uniquely poised to thrive in the TME and contribute to tumorigenesis. We describe how cellular metabolism and nutrient or metabolic communication shape Treg cell lineage identity and function in the TME. We also discuss the interplay between ICB and Treg cell metabolism and function, and highlight current strategies targeting Treg cell metabolism specifically in the TME. Understanding metabolic control of intratumoral Treg cells provides excellent opportunities to uncover new or combination therapies for cancer.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 25","pages":"2011-2024"},"PeriodicalIF":6.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03458-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226113","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: MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer","authors":"S. T. Guo,&nbsp;C. C. Jiang,&nbsp;G. P. Wang,&nbsp;Y. P. Li,&nbsp;C. Y. Wang,&nbsp;X. Y. Guo,&nbsp;R. H. Yang,&nbsp;Y. Feng,&nbsp;F. H. Wang,&nbsp;H. -Y Tseng,&nbsp;R. F. Thorne,&nbsp;L. Jin,&nbsp;X. D. Zhang","doi":"10.1038/s41388-025-03446-5","DOIUrl":"10.1038/s41388-025-03446-5","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 24","pages":"2008-2009"},"PeriodicalIF":6.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03446-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216501","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: DNA damage-induced translocation of mitochondrial factor HIGD1A into the nucleus regulates homologous recombination and radio/chemo-sensitivity","authors":"Bin Chen,&nbsp;Feng Xu,&nbsp;Yang Gao,&nbsp;Guanshuo Hu,&nbsp;Kaili Zhu,&nbsp;Huayi Lu,&nbsp;An Xu,&nbsp;Shaopeng Chen,&nbsp;Lijun Wu,&nbsp;Guoping Zhao","doi":"10.1038/s41388-025-03438-5","DOIUrl":"10.1038/s41388-025-03438-5","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 23","pages":"1891-1892"},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03438-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209022","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: Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation","authors":"Jian Gu,&nbsp;Xiaozhang Xu,&nbsp;Xiangyu Li,&nbsp;Lei Yue,&nbsp;Xiaowen Zhu,&nbsp;Qiuyang Chen,&nbsp;Ji Gao,&nbsp;Maruyama Takashi,&nbsp;Wenhu Zhao,&nbsp;Bo Zhao,&nbsp;Yue Zhang,&nbsp;Minjie Lin,&nbsp;Jinren Zhou,&nbsp;Yuan Liang,&nbsp;Shipeng Dai,&nbsp;Yufeng Pan,&nbsp;Qing Shao,&nbsp;Yu Li,&nbsp;Yiming Wang,&nbsp;Zibo Xu,&nbsp;Qufei Qian,&nbsp;Tianning Huang,&nbsp;Xiaofeng Qian,&nbsp;Ling Lu","doi":"10.1038/s41388-025-03439-4","DOIUrl":"10.1038/s41388-025-03439-4","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 24","pages":"2004-2007"},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03439-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209023","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":"An FGFR-p53 developmental signaling axis drives salivary cancer progression.","authors":"Adele M Musicant, Julia M R Billington, Jeffrey S Damrauer, Jennifer L Modliszewski, Luane J B Landau, Yi-Hsuan Tsai, Jay H Mehta, John Powers, Renee Betancourt, Radhika Sekhri, Ricardo J Padilla, Juan C Hernandez-Prera, D Neil Hayes, Trevor G Hackman, Omer Gokcumen, Sarah M Knox, Antonio L Amelio","doi":"10.1038/s41388-025-03444-7","DOIUrl":"10.1038/s41388-025-03444-7","url":null,"abstract":"<p><p>Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland malignancy. Here, we investigated transcriptomic profiles of human fetal and adult salivary glands and MEC tumors to assess programs involved in MEC progression. Molecular and genetic analyses revealed that MEC tumors and fetal salivary glands share proliferative and developmental gene expression profiles that implicate an FGFR-p53 signaling axis in salivary MEC progression. Based on these findings, we developed a genetically engineered mouse model of advanced MEC via targeted expression of the CRTC1-MAML2 oncogene in salivary ductal cells. Specifically, CRTC1-MAML2 expression combined with p53 dysregulation in salivary ducts rewires FGF signaling to drive formation of tumors with histological and molecular features of high-grade MEC. The combined bioinformatics and mouse modeling of this study demonstrate that salivary MEC progression is underpinned by reactivation of developmental signaling programs and suggests a role for FGFR targeted therapies in the treatment of high-grade MEC.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209021","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":"The lncRNA ST18-AS1 suppresses pancreatic cancer progression by enhancing ST18 mRNA stability through anchoring FUS in the cytoplasm.","authors":"Long Cheng, Hang Yu, Yujing Qin, Ruixin Wang, Tie Su, Gaoyuan Lyu, Zijian Huang, Hongtao Li, Yan Jin, Yilong Li, Gang Wang","doi":"10.1038/s41388-025-03455-4","DOIUrl":"https://doi.org/10.1038/s41388-025-03455-4","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is associated with a high mortality rate and short survival time. Long noncoding RNAs (lncRNAs) play a significant role in the progression of PDAC. However, prognostic lncRNAs associated with overall survival (OS) in patients with PDAC remain elusive. RNA sequencing was used to identify differential lncRNA expression between short-term and long-term PDAC patients. We identified a novel lncRNA (ENSG00000253924), termed ST18-AS1 (ST18-associated lncRNA), that is highly expressed in the tissues of long-term PDAC patients. High ST18-AS1 expression was correlated with favorable clinical outcomes, and the upregulation of ST18-AS1 expression in PDAC cell lines suppressed cell proliferation and promoted apoptosis both in vivo and in vitro. The key downstream target regulated by ST18-AS1 was Suppression of tumorigenicity 18 (ST18). We also found that ST18 expression was lower in PDAC tissues compared to non-tumorous adjacent tissues (NATs) and that higher ST18 expression was correlated with better clinical outcomes. Accordingly, the forced expression of ST18 inhibited proliferation and promoted apoptosis in tumor cells. Mechanistic studies showed that ST18-AS1 maintained the stability of ST18 mRNA by binding to Fused in sarcoma (FUS) and anchoring FUS in the cytoplasm. Overall, we identified ST18-AS1 as a novel biomarker that inhibits PDAC cell proliferation and promotes PDAC cell apoptosis through ST18. Targeting ST18-AS1/ST18 may be a potential therapeutic strategy for treating PDAC.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192091","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}