Oncogene最新文献

{"title":"Correction: Bioengineered tumor microenvironments with naked mole rats high-molecular-weight hyaluronan induces apoptosis in breast cancer cells","authors":"Yufang Zhao, Shupei Qiao, Xiaolu Hou, Hui Tian, Shuai Deng, Kangruo Ye, Yongzhan Nie, Xiongbiao Chen, Hongji Yan, Weiming Tian","doi":"10.1038/s41388-025-03506-w","DOIUrl":"10.1038/s41388-025-03506-w","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 32","pages":"2925-2926"},"PeriodicalIF":7.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03506-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708395","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":"Anti-cancer effect of interleukin-2 fused to flagellin expressed by tumor-targeting Salmonella.","authors":"Thanh Quang Tran, Taner Duysak, Kwangsoo Kim, Giang Chau Dang, Min-Hee Yi, Yoonjoo Choi, Jae Ho Cho, Jae-Ho Jeong, Hyon E Choy","doi":"10.1038/s41388-025-03504-y","DOIUrl":"https://doi.org/10.1038/s41388-025-03504-y","url":null,"abstract":"<p><p>Interleukin-2 (IL2) treatment has been explored as a potent immunotherapy agent, particularly for cancers, due to its ability to stimulate T cell proliferation and activity. However, significant challenges and limitations are associated with IL2 treatment, including its short half-life, systemic toxicity and side effects, and limited efficacy in solid tumors. In this study, we deployed an attenuated Salmonella Gallinarum (SG), an avian-specific pathogen capable of targeting tumor tissue, to express and secrete the IL2 using a bacterial flagellum type 3 secretion system (T3SS). Since the T3SS is used for the secretion of flagellin monomers (FliC), DNA of the human IL2 gene was fused to the SG fliC gene so that the fusion proteins would be exported together. A superb anti-cancer effect was observed when the SG expressing and secreting the FliC-IL2 fusion protein was injected into a syngeneic tumor mouse model with CT26 colorectal cancer via the tail vein. Within the fusion protein, the FliC moiety led to a selective increase in MHCII^highCD206^- M1-like macrophages, while the IL2 moiety promoted selective expansion of cytotoxic CD8⁺ T cells and NK cells, without expanding CD4⁺FoxP3⁺ regulatory T cells in the tumor microenvironment (TME). It was concluded that the local delivery of IL2 within the TME by cancer-targeting SG could overcome the limitations associated with IL2-based cancer immunotherapy.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708394","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: HMGB1 release and redox regulates autophagy and apoptosis in cancer cells","authors":"D. Tang,&nbsp;R. Kang,&nbsp;C- W. Cheh,&nbsp;K. M. Livesey,&nbsp;X. Liang,&nbsp;N. E. Schapiro,&nbsp;R. Benschop,&nbsp;L. J. Sparvero,&nbsp;A. A. Amoscato,&nbsp;K. J. Tracey,&nbsp;H. J. Zeh,&nbsp;M. T. Lotze","doi":"10.1038/s41388-025-03510-0","DOIUrl":"10.1038/s41388-025-03510-0","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 32","pages":"2927-2928"},"PeriodicalIF":7.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03510-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708396","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":"LINC00654 promotes ovarian cancer progression by facilitating nuclear export of HuR and stabilizing oncogenic mRNAs.","authors":"Cong Shen, Ruican Cao, Qiao Zhou, Tao Zhou, Tiantian Wu, Wenxin Gao, Gaigai Wang, Guannan Feng, Longwei Qiao, Ting Wang","doi":"10.1038/s41388-025-03500-2","DOIUrl":"https://doi.org/10.1038/s41388-025-03500-2","url":null,"abstract":"<p><p>Ovarian cancer (OC) remains a significant challenge in oncology due to its late diagnosis and poor prognosis. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in cancer biology. Herein, we reported that LINC00654 was highly expressed in OC tissues and correlated with poor patient prognosis. In addition, LINC00654 silencing restrained OC cell proliferation and migration in vitro and in vivo. Mechanically, LINC00654 was identified to directly interact with Human antigen R (HuR), a known RNA-binding protein, through RNA pull-down, RNA immunoprecipitation (RIP), and cross‑linking immunoprecipitation (CLIP). Further analysis revealed that LINC00654 could induce the translocation of HuR from the nucleus to the cytosol, where it regulated the stability of its target oncogenes, such as VASH2. The stabilization of VASH2 subsequently activated the TGF-β pathway, which is known to play a critical role in cancer progression. Taken together, these findings establish a specific mechanism by which LINC00654 interacts with HuR, facilitates its nuclear export, and stabilizes VASH2, thereby activating the TGF-β pathway and promoting OC progression. This insight into LINC00654's role in OC provides potential therapeutic targets for intervention.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682866","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":"Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.","authors":"Míriam Tarrado-Castellarnau, Carles Foguet, Josep Tarragó-Celada, Marc Palobart, Claudia Hernández-Carro, Jordi Perarnau, Erika Zodda, Ibrahim H Polat, Silvia Marin, Alejandro Suarez-Bonnet, Juan José Lozano, Mariia Yuneva, Timothy M Thomson, Marta Cascante","doi":"10.1038/s41388-025-03495-w","DOIUrl":"https://doi.org/10.1038/s41388-025-03495-w","url":null,"abstract":"<p><p>Several mechanisms of resistance of cancer cells to cyclin-dependent kinase inhibitors (CDKi) have been identified, including the upregulation of metabolic regulators such as glutaminase. However, whether such resistance mechanisms represent optimal targets has not been determined. Here, we have systematically analyzed metabolic reprogramming in colorectal cancer cells exposed to Palbociclib, a CDKi selectively targeting CDK4/6, or Telaglenastat, a selective glutaminase inhibitor. Through multiple approaches, we show that Palbociclib and Telaglenastat elicit complementary metabolic responses and are thus uniquely suited to counter the metabolic reprogramming induced by the reciprocal drug. As such, while Palbociclib induced reduced tumor growth in vivo, and Telaglenastat did not show a significant effect, the drug combination displayed a strong synergistic effect on tumor growth. Likewise, initial responses to Palbociclib were followed by signs of adaptation and resistance, which were prevented by combining Palbociclib with Telaglenastat. In conclusion, combination with Telaglenastat optimally forestalls acquired resistance to Palbociclib in cancer cells.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691166","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":"NSD2 promotes cell durotaxis and drives the transition from polycystic kidney disease to tubulocystic renal cell carcinoma through integrin/FAK/AKT signaling.","authors":"Wenxin Feng, Ningyuan Liu, Changwei Liu, Hanyu Rao, Zhuo Chen, Wei Zhang, Yue Xu, Rebiguli Aji, Ziyi Wang, Wei-Qiang Gao, Li Li","doi":"10.1038/s41388-025-03505-x","DOIUrl":"https://doi.org/10.1038/s41388-025-03505-x","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. NSD2 is an H3K36-specific di-methyltransferase that has been reported to participate in diverse biological processes and human tumors. However, its role in RCC remains unclear. Here, we found that NSD2 is highly expressed in RCC, which is associated with poor survival in RCC patients. NSD2 facilitates the transition from Myc-induced polycystic kidney disease to tubulocystic renal cell carcinoma (TCRCC), which is a rare RCC subtype with distinctive clinicopathologic and genetic characterizations. The mice with kidney-specific overexpression of MYC and NSD2 (KMN) display severe cyst burden at only 6 weeks of age, and develop into TCRCC at 12 weeks of age. Mechanistically, NSD2 transcriptionally upregulates the expressions of integrins (Itga4 and Itga11), to further activate the FAK/AKT pathway. In addition, we found that NSD2 enhances cell proliferation on the stiff matrix of PEGDA hydrogel. Moreover, inhibition of FAK signaling relieves the symptoms of KMN mice, and significantly rescues the enhanced cell proliferation caused by NSD2 overexpression in vitro. Together, our findings highlight an epigenetic mechanism by which NSD2 regulates TCRCC tumorigenesis through the integrin/FAK/AKT pathway. This study may also pave the way for the development of targeted, patient-tailored therapies for TCRCC patients with NSD2 amplification or high expression.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691167","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":"Unveiling the role of TAM-derived extracellular vesicles in glioma progression through Treg polarization and immune suppression.","authors":"Shoudan Zhang, Lin Zhang, Ning Guan, Xu Feng, Miaomiao Lu, Yanyun Wang","doi":"10.1038/s41388-025-03497-8","DOIUrl":"https://doi.org/10.1038/s41388-025-03497-8","url":null,"abstract":"<p><p>In the context of gliomas, tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) play crucial roles in shaping the tumor microenvironment (TME). This study focused on elucidating the mechanism by which TAM-derived extracellular vesicles (EVs) influence Treg differentiation and contribute to glioma progression. Through comprehensive single-cell RNA sequencing (scRNA-seq) analysis, the glioma TME was characterized by an abundance of TAMs exhibiting M2 polarization and increased Treg differentiation. Notably, TAM EVs were identified as potent inducers of Treg differentiation, with the downregulation of Bactericidal/Permeability-Increasing protein (BPI) being associated with this process. In vivo experiments utilizing a mouse model of glioma further demonstrated that TAM-derived EVs promoted glioma growth by enhancing Treg-mediated immunosuppression while dampening pro-inflammatory responses. This study highlights the critical role of TAM-derived EVs in modulating Treg differentiation and supporting glioma progression, suggesting that interventions targeting TAM EVs or regulating BPI expression could offer novel therapeutic avenues for combating immune suppression and inhibiting glioma development.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668040","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":"Targeted CRISPR approach reveals an essential role for neuropeptide Y receptor Y5 in Ewing sarcoma extrapulmonary metastasis.","authors":"Mina Adnani, Sung-Hyeok Hong, Susana Galli, Akanksha Mahajan, Congyi Lu, Nouran Abualsaud, Tyler Biermann, Yiwen Li, Andrea Rivera, Bethel S Sebsebie, Lindsay Caprio, Lindsey Kuwahara, Ewa Krawczyk, Jason U Tilan, Yichen Lee, Olga Rodriguez, Hongkun Wang, Lu Jin, Maureen Regan, Sonia de Assis, Christopher Albanese, Svetlana D Pack, Luciane R Cavalli, Joanna Kitlinska","doi":"10.1038/s41388-025-03493-y","DOIUrl":"https://doi.org/10.1038/s41388-025-03493-y","url":null,"abstract":"<p><p>Ewing sarcoma (ES) is a pediatric malignancy that lacks adequate therapies for its metastatic form. These tumors constitutively express neuropeptide Y (NPY) and its Y5 receptor (Y5R), which leads to elevated levels of the peptide in patients' serum. In animal models, xenografts secreting NPY metastasize to extrapulmonary niches, including bone; the phenotype associated with adverse prognosis in ES patients. To determine the role of the NPY/Y5R axis in ES extrapulmonary dissemination, we used a doxycycline-inducible CRISPR/Cas9 system to knockout Y5R in SK-ES-1 xenografts that metastasize to these niches. We have shown that metastases developing from heterogenous SK-ES-1/Y5R-sgRNA primary tumors in doxycycline-treated mice were initiated exclusively by SK-ES-1 clones with a functional NPY5R gene. Similarly, metastasis from wild type SK-ES-1 xenografts was associated with a selection of clones with NPY5R gene gain. In vitro assays identified Y5R-dependent ES cell motility driven by RhoA activation as the mechanism underlying the metastatic effects of NPY. In ES cell lines that secrete NPY, the autocrine NPY/Y5R loop was responsible for maintaining basal cell motility, while ES cells that do not release the peptide responded to the exogenous NPY. These data provide evidence for the crucial role of the NPY/Y5R axis in ES metastasis.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659738","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":"Steroid receptor coactivator-1 facilitates METTL3-mediated m6A modification by coactivating NF-κB and promotes the malignant progression of glioblastoma.","authors":"Liang Liu, Rui Wang, Ke Cheng, Chunmei Bai, Yuke Ji, Yifei Zhang, Haoran Yang, Miaomiao Gong, Fang Xie, Yongshun Zhao, Jinjin Pan, Yuhui Yuan","doi":"10.1038/s41388-025-03494-x","DOIUrl":"https://doi.org/10.1038/s41388-025-03494-x","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an incurable disease with a poor prognosis. However, the potential impact of steroid receptor coactivator-1 (SRC-1) on N6-methyladenosine (m6A) RNA modification and its role in promoting malignant progression in GBM remain unclear. The relationship between SRC-1 and the m6A \"writer\" protein, methyltransferase 3 (METTL3), was analyzed using data from the CGGA database. Dot blot and MeRIP‒qPCR were performed to evaluate the effects of SRC-1 knockdown or overexpression on the level of m6A modification in GBM. The biological functions of SRC-1 in regulating METTL3 in GBM were evaluated by assessing its effects on proliferation, migration, cell cycle, colony formation, and apoptosis in vitro and the tumor volume/weight of nude mice xenografted with GBM cells in vivo. Co-IP, immunofluorescence, dual-luciferase, and ChIP‒qPCR assays were subsequently conducted. By analyzing the CGGA database, we determined that SRC-1 has a close positive relationship with METTL3 in GBM. SRC-1 significantly increased the m6A RNA modification level in GBM, SRC-1 knockdown markedly inhibited c-Myc m6A methylation and mRNA stability by suppressing METTL3, and SRC-1 overexpression led to hypermethylation by increasing METTL3. SRC-1 knockdown inhibited the proliferation, migration, apoptosis resistance, and S and G2/M phases of GBM cells in vitro. Mechanically, SRC-1 interacted with the heterodimer of NF-κB p50/p65, whereby p65 activated METTL3 by directly binding to a specific region of its promoter (+18 to +27 bp), thereby increasing the m6A modification of c-Myc and ultimately promoting GBM progression. Importantly, both SRC-1 knockdown and treatment with bufalin, an SRC inhibitor, reduced GBM progression. In conclusion, this study provides the first comprehensive evidence that SRC-1 facilitates GBM progression by binding to NF-κB and regulating METTL3-mediated m6A modification of c-Myc, offering new insights into potential therapeutic strategies for GBM. Schematic diagram of the mechanism revealed in this research. SRC-1 regulates METTL3-mediated m6A RNA modification of c-Myc to promote GBM progression by binding to the NF-κB transcription factor. Created in BioRender. https://BioRender.com .</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643097","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":"Targeting CSF-1 signaling between tumor cells and macrophages at TMEM doorways inhibits breast cancer dissemination.","authors":"Camille L Duran, Chinmay R Surve, Xianjun Ye, Xiaoming Chen, Yu Lin, Allison S Harney, Yarong Wang, Ved P Sharma, E Richard Stanley, Dianne Cox, John C McAuliffe, David Entenberg, Maja H Oktay, John S Condeelis","doi":"10.1038/s41388-025-03485-y","DOIUrl":"https://doi.org/10.1038/s41388-025-03485-y","url":null,"abstract":"<p><p>Tumor cell intravasation is essential for metastatic dissemination, but its exact mechanism is incompletely understood. We have previously shown that in breast cancer, the direct and stable association of a tumor cell expressing Mena, a Tie2^hi/VEGF^hi macrophage, and a vascular endothelial cell, creates an intravasation portal, called a \"tumor microenvironment of metastasis\" (TMEM) doorway, for tumor cell intravasation, leading to dissemination to distant sites. The density of TMEM doorways, also called TMEM doorway score, is a clinically validated prognostic marker of distant metastasis in breast cancer patients. Although we know that tumor cells utilize TMEM doorway-associated transient vascular openings to intravasate, the precise signaling mechanisms involved in TMEM doorway function are only partially understood. Using two mouse models of breast cancer and an in vitro assay of intravasation, we report that CSF-1 secreted by the TMEM doorway tumor cell stimulates local secretion of VEGF-A from the Tie2^hi TMEM doorway macrophage, leading to the dissociation of endothelial junctions between TMEM doorway-associated endothelial cells, supporting tumor cell intravasation. Acute blockade of CSF-1/CSF-1R signaling decreases macrophage VEGF-A secretion as well as TMEM doorway-associated vascular opening, tumor cell trans-endothelial migration, and dissemination. These new insights into signaling events regulating TMEM doorway function should be explored further as treatment strategies for metastatic disease.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619709","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}