Oncogene最新文献_第3页

Wnt target IQGAP3 promotes Wnt signaling via disrupting Axin1-CK1α interaction. Wnt靶点IQGAP3通过破坏Axin1-CK1α相互作用促进Wnt信号传导。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-19 DOI: 10.1038/s41388-025-03512-y

Muhammad Bakhait Rahmat, Aashiq Hussain, Yu Xuan Teh, Bibek Dutta, Sumedha Pundrik, Dennis Kappei, Yoshiaki Ito

引用次数: 0

Editorial Expression of Concern: ATM is a target for positive regulation by E2F-1 编辑表达关注：ATM是E2F-1积极监管的目标。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-19 DOI: 10.1038/s41388-025-03551-5

Eli Berkovich, Doron Ginsberg

引用次数: 0

Membrane flexibility induced by BST2 contributes to radioresistance in glioblastoma. BST2诱导的膜柔韧性有助于胶质母细胞瘤的放射抵抗。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-18 DOI: 10.1038/s41388-025-03544-4

Haksoo Lee, Dahye Kim, Byeongsoo Kim, Eunguk Shin, Hyunkoo Kang, Jae-Myung Lee, HyeSook Youn, BuHyun Youn

{"title":"Membrane flexibility induced by BST2 contributes to radioresistance in glioblastoma.","authors":"Haksoo Lee, Dahye Kim, Byeongsoo Kim, Eunguk Shin, Hyunkoo Kang, Jae-Myung Lee, HyeSook Youn, BuHyun Youn","doi":"10.1038/s41388-025-03544-4","DOIUrl":"10.1038/s41388-025-03544-4","url":null,"abstract":"Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis due to its resistance to radiotherapy. Epidermal growth factor receptor variant III (EGFRvIII), a common mutation in GBM, promotes radioresistance through ligand-independent activation. We hypothesized that membrane flexibility influences EGFRvIII activation and enhances resistance. Bone marrow stromal antigen 2 (BST2, CD317, or TETHERIN) was identified as a key mediator linking membrane dynamics to EGFRvIII-driven survival signaling. Radiation-induced changes in membrane flexibility amplified BST2 activity, stabilizing lipid rafts and promoting EGFRvIII clustering. Pharmacological inhibition of BST2 with arbutin, an FDA-approved compound, disrupted this mechanism, increasing GBM radiosensitivity by enhancing mitochondrial reactive oxygen species (ROS) production and apoptosis. Additionally, BST2 downregulation impaired de novo lipogenesis and reduced lipid droplet accumulation, highlighting its role in metabolic reprogramming. In orthotopic xenograft models, BST2 inhibition suppressed tumor growth and prolonged survival. These findings establish BST2 as a key regulator of membrane-driven radioresistance in GBM. Targeting BST2-mediated membrane remodeling may provide a novel therapeutic strategy to enhance radiotherapy efficacy.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874333","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}

引用次数: 0

ALDH1A3 promotes aggressive basal-like pancreatic cancer through an AP-1/RUNX2 enhancer network. ALDH1A3通过AP-1/RUNX2增强子网络促进侵袭性基底样胰腺癌。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-08 DOI: 10.1038/s41388-025-03530-w

Xiaoping Zou, Shuang Nie, Jing Cao, Mengyue Shi, Kathleen Schuck, Zhao Shi, Lingling Zhang, Hongzhen Li, Yifeng Sun, Chao Fang, Jingxiong Hu, Yiqi Niu, Yuanyuan Yu, Zhiheng Zhang, Chao Li, Mingyue Hu, Lei Wang, Kuirong Jiang, Zipeng Lu, Jan Akkan, Susanne Raulefs, Christoph Kahlert, Susanne Roth, Ingrid Herr, Yuan Wan, Andre Mihaljevic, Xuetian Qian, Qi Zhang, Maggie Haitian Wang, Jörg Kleeff, Helmut Friess, Zuguang Gu, Christoph W Michalski, Shanshan Shen, Bo Kong

{"title":"ALDH1A3 promotes aggressive basal-like pancreatic cancer through an AP-1/RUNX2 enhancer network.","authors":"Xiaoping Zou, Shuang Nie, Jing Cao, Mengyue Shi, Kathleen Schuck, Zhao Shi, Lingling Zhang, Hongzhen Li, Yifeng Sun, Chao Fang, Jingxiong Hu, Yiqi Niu, Yuanyuan Yu, Zhiheng Zhang, Chao Li, Mingyue Hu, Lei Wang, Kuirong Jiang, Zipeng Lu, Jan Akkan, Susanne Raulefs, Christoph Kahlert, Susanne Roth, Ingrid Herr, Yuan Wan, Andre Mihaljevic, Xuetian Qian, Qi Zhang, Maggie Haitian Wang, Jörg Kleeff, Helmut Friess, Zuguang Gu, Christoph W Michalski, Shanshan Shen, Bo Kong","doi":"10.1038/s41388-025-03530-w","DOIUrl":"https://doi.org/10.1038/s41388-025-03530-w","url":null,"abstract":"The basal-like transcriptional subtype of pancreatic ductal adenocarcinoma (PDAC) is linked to therapy resistance and poor prognosis. The cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) is a critical enzyme in acetaldehyde metabolism, but the interconnection to the basal-like subtype is poorly understood. Here, we identified ALDH1A3 as a key gene, which correlates with reduced survival and increased tumor growth. Functional studies revealed interaction of ALDH1A3 with genes like FAM3C, MCC, PMEPA1, and IRS2, forming a network driving PDAC progression. Chromatin profiling showed that ALDH1A3 affects acetylation of histone 3, mediating AP-1 activity, particularly via FOS family members, activating oncogenic pathways such as MAPK and TNF signaling. RUNX2 emerged as a therapeutic target within this network, as its knockdown disrupted MAPK signaling and reduced tumor growth. These findings emphasize the role of ALDH1A3 in linking nuclear metabolic-epigenetic programming in basal-like PDAC, highlighting it as a promising therapeutic target for novel treatment strategies.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804490","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}

引用次数: 0

Correction: CPT1A-mediated fatty acid oxidation promotes colorectal cancer cell metastasis by inhibiting anoikis 更正：cpt1a介导的脂肪酸氧化通过抑制肿瘤的发生促进结直肠癌细胞转移。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-07 DOI: 10.1038/s41388-025-03508-8

Ying-nan Wang, Zhao-lei Zeng, Jiahuan Lu, Yun Wang, Ze-xian Liu, Ming-ming He, Qi Zhao, Zi-xian Wang, Ting Li, Yun-xin Lu, Qi-nian Wu, Kai Yu, Feng Wang, Heng-Ying Pu, Bo Li, Wei-hua Jia, Ming shi, Dan Xie, Tie-bang Kang, Peng Huang, Huai-qiang Ju, Rui-hua Xu

引用次数: 0

LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1 LIMK2通过激活mst4介导的NPM1磷酸化，促进中心体聚集和癌症进展。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-07 DOI: 10.1038/s41388-025-03518-6

Jie Tian, Shihui Liu, Yunqing Zhang, Huajie Jia, Wenna Nie, Ran Yang, Mengmeng Ge, Kangdong Liu, Mengqiu Song, Zigang Dong

{"title":"LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1","authors":"Jie Tian, Shihui Liu, Yunqing Zhang, Huajie Jia, Wenna Nie, Ran Yang, Mengmeng Ge, Kangdong Liu, Mengqiu Song, Zigang Dong","doi":"10.1038/s41388-025-03518-6","DOIUrl":"10.1038/s41388-025-03518-6","url":null,"abstract":"Centrosome amplification, a hallmark of diverse malignancies, enables cancer cell survival through centrosome clustering during mitosis, presenting a promising therapeutic target for selective elimination of cancer cells with supernumerary centrosomes. While the regulatory mechanisms underlying centrosome clustering remain poorly understood, our study identifies LIM kinase 2 (LIMK2) as a critical regulator of this process, demonstrating cancer correlation with tumor progression. Mechanistically, LIMK2 phosphorylates mammalian sterile-20-like kinase 4 (MST4) at threonine 178 (T178), activating its kinase function. Activated MST4 subsequently binds and phosphorylates nucleophosmin 1 (NPM1) at T95, a modification essential for centrosome clustering and tumor cell proliferation. Genetic depletion of NPM1 disrupts centrosome clustering and suppresses malignant growth. In vivo studies revealed that LIMK2 knockout significantly attenuates 4-nitroquinoline-1-oxide (4NQO) induced esophageal tumorigenesis in murine models. Therapeutic targeting of LIMK2 through shRNA-mediated knock down or pharmacological inhibition (CRT0105950) suppresses centrosome clustering by preventing “pseudo-bipolar” spindle formation, inducing mitosis arrest. This centrosome de-clustering promotes multipolar spindle assembly, ultimately triggering apoptotic cell death. Notably, CRT0105950 treatment effectively suppressed cell-derived xenograft tumor growth. Our findings elucidate the pivotal role of the LIMK2/MST4/NPM1 pathway in cancer progression and establish a novel therapeutic paradigm for broad-spectrum anticancer intervention.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 38","pages":"3625-3639"},"PeriodicalIF":7.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03518-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799683","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}

引用次数: 0

Retraction Note: VPAC1 couples with TRPV4 channel to promote calcium-dependent gastric cancer progression via a novel autocrine mechanism 注：VPAC1与TRPV4通道通过一种新的自分泌机制促进钙依赖性胃癌的进展。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-06 DOI: 10.1038/s41388-025-03525-7

Bo Tang, Jilin Wu, Michael X. Zhu, Xuemei Sun, Jingjing Liu, Rui Xie, Tobias Xiao Dong, Yufeng Xiao, John M. Carethers, Shiming Yang, Hui Dong

引用次数: 0

Retraction Note: Fermitin family member 2 promotes melanoma progression by enhancing the binding of p-α-Pix to Rac1 to activate the MAPK pathway 备注：fermittin家族成员2通过增强p-α-Pix与Rac1的结合激活MAPK通路来促进黑色素瘤的进展。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-05 DOI: 10.1038/s41388-025-03524-8

Shaobin Huang, Wuguo Deng, Peng Wang, Yue Yan, Chuanbo Xie, Xiaoling Cao, Miao Chen, Changlin Zhang, Dingbo Shi, Yunxian Dong, Pu Cheng, Hailin Xu, Wenkai Zhu, Zhicheng Hu, Bing Tang, Jiayuan Zhu

引用次数: 0

MUC1-C auto-regulatory complex with EBNA1 is responsible for latent Epstein-Barr virus-associated gastric cancer progression MUC1-C与EBNA1的自调节复合体是潜在的eb病毒相关胃癌进展的原因。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-05 DOI: 10.1038/s41388-025-03519-5

Hiroki Ozawa, Yin Wang, Henry G. Withers, Naoki Haratake, Ayako Nakashoji, Atrayee Bhattacharya, Atsushi Fushimi, Chie Kikutake, Kazuhiro Yamanoi, Shaowen White, Keyi Wang, Tatsuaki Daimon, Keisuke Shigeta, Kazumasa Fukuda, Hirofumi Kawakubo, Yuko Kitagawa, Mark D. Long, Benjamin E. Gewurz, Donald Kufe

{"title":"MUC1-C auto-regulatory complex with EBNA1 is responsible for latent Epstein-Barr virus-associated gastric cancer progression","authors":"Hiroki Ozawa, Yin Wang, Henry G. Withers, Naoki Haratake, Ayako Nakashoji, Atrayee Bhattacharya, Atsushi Fushimi, Chie Kikutake, Kazuhiro Yamanoi, Shaowen White, Keyi Wang, Tatsuaki Daimon, Keisuke Shigeta, Kazumasa Fukuda, Hirofumi Kawakubo, Yuko Kitagawa, Mark D. Long, Benjamin E. Gewurz, Donald Kufe","doi":"10.1038/s41388-025-03519-5","DOIUrl":"10.1038/s41388-025-03519-5","url":null,"abstract":"Latent Epstein-Barr Virus (EBV) infection promotes cancers derived from B-lymphocytes and epithelial cells by mechanisms that largely remain unclear. EBV-encoded nuclear antigen 1 (EBNA1) is uniformly expressed in EBV-associated cancers; however, how EBNA1 contributes to cancer progression is not known. The MUC1 gene evolved in mammals to protect barrier tissues from viral infections. We report that MUC1 is upregulated in EBV-associated gastric cancers (EBVaGCs). Our results demonstrate that EBNA1 and the oncogenic MUC1-C subunit form an auto-regulatory complex that controls expression of EBNA1, MUC1-C and host cellular genes. EBNA1 appropriates MUC1-C to (i) induce DNA methyltransferase (DNMT) expression and DNA methylation, (ii) suppress CDKN1A encoding p21 to promote proliferation, and (iii) upregulate survivin to confer survival. MUC1-C is also co-opted for localization of EBNA1 in chromatin, expression of EBV latency genes and suppression of lytic genes. Targeting MUC1-C thereby induces the switch of EBV latency to activation of the lytic phase. We further demonstrate that MUC1-C is necessary for EBVaGC stem cell (CSC) state as evidenced by regulation of NOTCH stemness genes and self-renewal capacity. These findings and the demonstration that EBV positivity has no significant effect on survival of patients with GCs indicate that EBNA1 exploits MUC1-C to maintain EBV latency and that prolonged activation of MUC1-C in response to chronic EBV infection promotes EBVaGC malignant progression.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 38","pages":"3609-3624"},"PeriodicalIF":7.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03519-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789596","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}

引用次数: 0

The CIC::DUX4 oncoprotein maintains DNA integrity through direct regulation of the catalytic subunit of DNA polymerase epsilon (POLE) CIC::DUX4癌蛋白通过直接调控DNA聚合酶epsilon （POLE）的催化亚基来维持DNA的完整性。

IF 7.3 1区医学

Oncogene Pub Date : 2025-08-04 DOI: 10.1038/s41388-025-03507-9

Zeinab Kosibaty, Cuyler Luck, Ross A. Okimoto

{"title":"The CIC::DUX4 oncoprotein maintains DNA integrity through direct regulation of the catalytic subunit of DNA polymerase epsilon (POLE)","authors":"Zeinab Kosibaty, Cuyler Luck, Ross A. Okimoto","doi":"10.1038/s41388-025-03507-9","DOIUrl":"10.1038/s41388-025-03507-9","url":null,"abstract":"Transcription factor (TF) fusion oncoproteins represent cancer-specific alterations that arise from chromosomal rearrangements. Through target gene recognition, TF fusions can disseminate transcriptional responses that collectively work to drive tumorigenesis. Thus, identifying the molecular targets that operate as a disease-driving network can potentially uncover key actionable dependencies. We have taken this strategy to dissect the underlying biological mechanism by which CIC::DUX4, a fusion oncoprotein associated with dismal outcomes, drives sarcomagenesis. We and others have defined a CIC::DUX4 fusion-mediated network that dysregulates cell-cycle and DNA replication checkpoints. Specifically, CIC::DUX4-mediated CCNE1 upregulation compromises the G1/S transition, leading to high DNA replication stress and conferring a dependence on the G2/M checkpoint kinase, WEE1. WEE1 provides a molecular brake to enable effective DNA repair prior to mitotic entry. Importantly, the mechanism by which CIC::DUX4 regulates DNA repair remains unknown. Here we show that the catalytic subunit of DNA polymerase epsilon (POLE) is essential for DNA integrity and cellular division in CIC::DUX4 sarcoma. Mechanistically, POLE loss increases DNA damage and induces p21-mediated cellular senescence to limit CIC::DUX4 tumor growth in vitro and tumor formation in vivo. Collectively, we credential POLE as a CIC::DUX4 target and further characterize a functional network through which CIC::DUX4 operates to drive tumor progression and survival.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 38","pages":"3598-3608"},"PeriodicalIF":7.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41388-025-03507-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784916","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}

引用次数: 0