Oncogene最新文献

{"title":"Hypoxia-dependent recruitment of error-prone DNA polymerases to genome replication.","authors":"Ran Yehuda, Ido Dromi, Yishai Levin, Thomas Carell, Nicholas Geacintov, Zvi Livneh","doi":"10.1038/s41388-024-03192-0","DOIUrl":"https://doi.org/10.1038/s41388-024-03192-0","url":null,"abstract":"<p><p>Hypoxia is common in tumors and is associated with cancer progression and drug resistance, driven, at least in part, by genetic instability. Little is known on how hypoxia affects Translesion DNA Synthesis (TLS), in which error-prone DNA polymerases bypass lesions, thereby maintaining DNA continuity at the price of increased mutations. Here we show that under acute hypoxia, PCNA monoubiquitination, a key step in TLS, and expression of error-prone DNA polymerases increased under regulation of the HIF1α transcription factor. Knocking-down expression of DNA polymerase η, or using PCNA ubiquitination-resistant cells, inhibited genomic DNA replication specifically under hypoxia, and iPOND analysis revealed massive recruitment of TLS DNA polymerases to nascent DNA under hypoxia, uncovering a dramatic involvement of error-prone DNA polymerases in genomic replication. Of note, expression of TLS-polymerases correlates with VEGFA (primary HIF1α target) in a database of renal cell carcinoma, a cancer which accumulates HIF1α. Our results suggest that the tumor microenvironment can lead the cell to forgo, to some extent, the fast and accurate canonical DNA polymerases, for the more flexible and robust, but low-fidelity TLS DNA polymerases. This might endow cancer cells with resilience to overcome replication stress, and mutability to escape the immune system and chemotherapeutic drugs.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522603","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":"Transcriptional regulation by MYC: an emerging new model.","authors":"Simon T Jakobsen, Rasmus Siersbæk","doi":"10.1038/s41388-024-03174-2","DOIUrl":"https://doi.org/10.1038/s41388-024-03174-2","url":null,"abstract":"<p><p>The transcription factor MYC has long been recognized for its pivotal role in transcriptional regulation of genes fundamental for cellular processes such as cell cycle, apoptosis, and metabolism. Dysregulation of MYC activity is implicated in various diseases, most notably cancer, where MYC drives uncontrolled cell proliferation and growth. Despite its significant role in cancer biology, targeting MYC for therapeutic purposes has been challenging due to its highly disordered protein structure. Hence, recent research efforts have focused on identifying the transcriptional mechanisms underlying MYC function to identify alternative strategies for intervention. This review summarizes recent advances in our understanding of how MYC orchestrates context-dependent and -independent gene-regulatory activities in cancer. Based on recent insights into the gene-regulatory function of MYC at enhancers, we propose an extension of the gene-specific affinity model. In this revised model, MYC enhancer activity drives context-specific gene programs that are distinct from the ubiquitously activated set of core MYC target genes driven by MYC promoter binding. The increased MYC enhancer activity in cancer and the distinct function of MYC at these regions compared to promoters may provide an opportunity for designing therapeutic approaches selectively targeting MYC enhancer activity in cancer cells.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522604","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":"Dependence of PAX3-FOXO1 chromatin occupancy on ETS1 at important disease-promoting genes exposes new targetable vulnerability in Fusion-Positive Rhabdomyosarcoma.","authors":"Joseph Hsieh, Etienne P Danis, Charles R Owens, Janet K Parrish, Nathan L Nowling, Arthur R Wolin, Stephen Connor Purdy, Sheera R Rosenbaum, Atma M Ivancevic, Edward B Chuong, Heide L Ford, Paul Jedlicka","doi":"10.1038/s41388-024-03201-2","DOIUrl":"https://doi.org/10.1038/s41388-024-03201-2","url":null,"abstract":"<p><p>Rhabdomyosarcoma (RMS), a malignancy of impaired myogenic differentiation, is the most common soft tissue pediatric cancer. PAX3-FOXO1 oncofusions drive the majority of the clinically more aggressive fusion-positive rhabdomyosarcoma (FP-RMS). Recent studies have established an epigenetic basis for PAX3-FOXO1-driven oncogenic processes. However, details of PAX3-FOXO1 epigenetic mechanisms, including interactions with, and dependence on, other chromatin and transcription factors, are incompletely understood. We previously identified a novel disease-promoting epigenetic axis in RMS, involving the histone demethylase KDM3A and the ETS1 transcription factor, and demonstrated that this epigenetic axis interfaces with PAX3-FOXO1 both phenotypically and transcriptomically, including co-regulation of biological processes and genes important to FP-RMS progression. In this study, we demonstrate that KDM3A and ETS1 colocalize with PAX3-FOXO1 to enhancers of important disease-promoting genes in FP-RMS, including FGF8, IL4R, and MEST, as well as PODXL, which we define herein as a new FP-RMS-promoting gene. We show that ETS1, which is induced by both PAX3-FOXO1 and KDM3A, exists in complex with PAX3-FOXO1, and augments PAX3-FOXO1 chromatin occupancy. We further show that the PAX3-FOXO1/ETS1 complex can be disrupted by the clinically relevant small molecule inhibitor YK-4-279. YK-4-279 displaces PAX3-FOXO1 from chromatin and interferes with PAX3-FOXO1-dependent gene regulation, resulting in potent inhibition of growth and invasive properties in FP-RMS, along with downregulation of FGF8, IL4R, MEST and PODXL expression. We additionally show that, in some FP-RMS, KDM3A also increases PAX3-FOXO1 levels. Together, our studies illuminate mechanisms of action of the KDM3A/ETS1 regulatory module, and reveal novel targetable mechanisms of PAX3-FOXO1 chromatin complex regulation, in FP-RMS.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505251","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: Editorial Expression of Concern: Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer","authors":"Simone Fulda,&nbsp;Martin U. Kuüfer,&nbsp;Eric Meyer,&nbsp;Frans van Valen,&nbsp;Barbara Dockhorn-Dworniczak,&nbsp;Klaus-Michael Debatin","doi":"10.1038/s41388-024-03204-z","DOIUrl":"10.1038/s41388-024-03204-z","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"43 46","pages":"3417-3417"},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03204-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505250","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":"USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer","authors":"Michaela Reissland,&nbsp;Oliver Hartmann,&nbsp;Saskia Tauch,&nbsp;Jeroen M. Bugter,&nbsp;Cristian Prieto-Garcia,&nbsp;Clemens Schulte,&nbsp;Sinah Loebbert,&nbsp;Daniel Solvie,&nbsp;Eliya Bitman-Lotan,&nbsp;Ashwin Narain,&nbsp;Anne-Claire Jacomin,&nbsp;Christina Schuelein-Voelk,&nbsp;Carmina T. Fuss,&nbsp;Nikolett Pahor,&nbsp;Carsten Ade,&nbsp;Viktoria Buck,&nbsp;Michael Potente,&nbsp;Vivian Li,&nbsp;Gerti Beliu,&nbsp;Armin Wiegering,&nbsp;Tom Grossmann,&nbsp;Martin Eilers,&nbsp;Elmar Wolf,&nbsp;Hans Maric,&nbsp;Mathias Rosenfeldt,&nbsp;Madelon M. Maurice,&nbsp;Ivan Dikic,&nbsp;Peter Gallant,&nbsp;Amir Orian,&nbsp;Markus E. Diefenbacher","doi":"10.1038/s41388-024-03141-x","DOIUrl":"10.1038/s41388-024-03141-x","url":null,"abstract":"The contribution of deubiquitylating enzymes (DUBs) to β-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes β-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring β-catenin degradation. However, in APC-truncated cancer cells USP10 binds to β-catenin, increasing its stability which is critical for maintaining an undifferentiated tumour identity. Elimination of USP10 reduces the expression of WNT and stem cell signatures and induces the expression of differentiation genes. Remarkably, silencing of USP10 in murine and patient-derived CRC organoids established that it is essential for NOTUM signalling and the APC super competitor-phenotype, reducing tumorigenic properties of APC-truncated CRC. These findings are clinically relevant as patient-derived organoids are highly dependent on USP10, and abundance of USP10 correlates with poorer prognosis of CRC patients. Our findings reveal, therefore, a role for USP10 in CRC cell identity, stemness, and tumorigenic growth by stabilising β-Catenin, leading to aberrant WNT signalling and degradation resistant tumours. Thus, USP10 emerges as a unique therapeutic target in APC truncated CRC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"43 50","pages":"3645-3659"},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03141-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505255","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":"TMSB4Y restrains sphingomyelin synthesis via de novo purine synthesis to exert a tumor suppressor function in male esophageal squamous cell carcinoma","authors":"Tongyang Gong,&nbsp;Wanyuan Sun,&nbsp;Xukun Li,&nbsp;Jiahui Cai,&nbsp;Ning Zhao,&nbsp;Minyi Lu,&nbsp;Juan Xu,&nbsp;Zhihua Liu,&nbsp;Hongyan Chen","doi":"10.1038/s41388-024-03193-z","DOIUrl":"10.1038/s41388-024-03193-z","url":null,"abstract":"Y chromosome genes play a vital role in sex difference of cancer. The dysregulation and functional implications of Y chromosome genes in esophageal squamous cell carcinoma (ESCC) remains elusive. Here, we analyze the Y chromosome gene signature and identify TMSB4Y as an emerging prognostic predictor in male ESCC. Functional analyses show that TMSB4Y inhibits the proliferation, invasion and metastasis of male ESCC cells. Mechanistically, we demonstrate that TMSB4Y interacts with PAICS, wherein TMSB4Y disrupts the formation of the PAICS octamer to inhibit purine de novo synthesis, leading to a decrease in the AMP/ATP ratio, subsequently impeding AMPK phosphorylation. Furthermore, we uncover a regulatory cascade orchestrated by the TMSB4Y/PAICS-AMPK axis, which exerts a suppressive effect on sphingomyelin metabolism by inhibiting the expression of sphingomyelin synthases (SMSs). Notably, Malabaricone C, an inhibitor of SMS1 and SMS2, effectively suppresses male ESCC cell proliferation and xenograft tumor growth. Collectively, these findings reveal the regulation of sphingomyelin metabolism by TMSB4Y/PAICS-AMPK axis and underscore the potential of targeting SMSs as a promising therapeutic approach for the treatment of male ESCC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"43 50","pages":"3660-3672"},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505254","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":"PTPRZ1 dephosphorylates and stabilizes RNF26 to reduce the efficacy of TKIs and PD-1 blockade in ccRCC","authors":"Yongkang Ma,&nbsp;Wei Li,&nbsp;Xinlin Liu,&nbsp;Weilin Peng,&nbsp;Bei Qing,&nbsp;Shangqing Ren,&nbsp;Wentao Liu,&nbsp;Xiaobing Chen","doi":"10.1038/s41388-024-03198-8","DOIUrl":"10.1038/s41388-024-03198-8","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, often exhibits resistance to tyrosine kinase inhibitors (TKIs) when used as monotherapy. However, the integration of PD-1 blockade with TKIs has significantly improved patient survival, making it a leading therapeutic strategy for ccRCC. Despite these advancements, the efficacy of this combined therapy remains suboptimal, necessitating a deeper understanding of the underlying regulatory mechanisms. Through comprehensive analyses, including mass spectrometry, RNA sequencing, lipidomic profiling, immunohistochemical staining, and ex vivo experiments, we explored the interaction between PTPRZ1 and RNF26 and its impact on ccRCC cell behavior. Our results revealed a unique interaction where PTPRZ1 stabilized RNF26 protein expression by dephosphorylating it at the Y432 site. The modulation of RNF26 levels by PTPRZ1 was found to be mediated through the proteasome pathway. Additionally, PTPRZ1, via its interaction with RNF26, activated the TNF/NF-κB signaling pathway, thereby promoting cell proliferation, angiogenesis, and lipid metabolism in ccRCC cells. Importantly, inhibiting PTPRZ1 enhanced the sensitivity of ccRCC to TKIs and PD-1 blockade, an effect that was attenuated when RNF26 was simultaneously knocked down. These findings highlight the critical role of the PTPRZ1-RNF26 axis in ccRCC and suggest that combining PTPRZ1 inhibitors with current TKIs and PD-1 blockade therapies could significantly improve treatment outcomes for ccRCC patients.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"43 50","pages":"3633-3644"},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505253","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":"KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development","authors":"Samantha L. Tinsley,&nbsp;Ella Rose D. Chianis,&nbsp;Rebecca A. Shelley,&nbsp;Gaganpreet K. Mall,&nbsp;Alisha Dhiman,&nbsp;Garima Baral,&nbsp;Harish Kothandaraman,&nbsp;Mary C. Thoma,&nbsp;Isabel A. English,&nbsp;Colin J. Daniel,&nbsp;Luis Carlos Sanjuan Acosta,&nbsp;Luis Solorio,&nbsp;Nadia Atallah Lanman,&nbsp;Marina Pasca di Magliano,&nbsp;Goutham Narla,&nbsp;Emily C. Dykhuizen,&nbsp;Rosalie C. Sears,&nbsp;Brittany L. Allen-Petersen","doi":"10.1038/s41388-024-03196-w","DOIUrl":"10.1038/s41388-024-03196-w","url":null,"abstract":"Oncogenic mutations in KRAS are present in ~95% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and are considered the initiating event of pancreatic intraepithelial neoplasia (PanIN) precursor lesions. While it is well established that KRAS mutations drive the activation of oncogenic kinase cascades during pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (PP2A) has been implicated in suppressing KRAS-driven cellular transformation and low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC. In the current study, we demonstrate that KRASG12D induces the expression of an endogenous inhibitor of PP2A activity, Cancerous Inhibitor of PP2A (CIP2A), and phosphorylation of the PP2A substrate, c-MYC. Consistent with these findings, KRASG12D sequestered the specific PP2A subunit responsible for c-MYC degradation, B56α, away from the active PP2A holoenzyme in a CIP2A-dependent manner. During PDAC initiation in vivo, knockout of B56α promoted KRASG12D tumorigenesis by accelerating acinar-to-ductal metaplasia (ADM) and the formation of PanIN lesions. The process of ADM was attenuated ex vivo in response to pharmacological re-activation of PP2A utilizing direct small molecule activators of PP2A (SMAPs). Together, our results suggest that suppression of PP2A-B56α through KRAS signaling can promote the MYC-driven initiation of pancreatic tumorigenesis.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"43 50","pages":"3673-3687"},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03196-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505252","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":"Zinc ions activate AKT and promote prostate cancer cell proliferation via disrupting AKT intramolecular interaction.","authors":"Kangjunjie Wang, Min Chen, Shukun Yan, Ying Han, Huairui Yuan, Qiuli Liu, Dayun Lu, Long Li, Kaihua Wang, Fen Liu, Qianqian Li, Dakui Luo, Jun Jiang, Hu Zhou, Yong Chen, Jun Qin, Daming Gao","doi":"10.1038/s41388-024-03195-x","DOIUrl":"https://doi.org/10.1038/s41388-024-03195-x","url":null,"abstract":"<p><p>Prostate is a zinc rich organ and the physiological function of the abundant zinc ions is relatively less understood. AKT kinase is a pivotal regulator downstream of cytokines, growth factors and other extracellular stimuli, and the attachment of its PH domain to PtdIns-3,4,5-P3 (PIP3) and the subsequent phosphorylation of its kinase domain by PDPK1 are considered important for its activation. Herein, we report a regulatory mechanism of AKT kinase by zinc ions. Mechanistically, zinc ions directly bind to AKT and facilitate AKT activation through disrupting the interaction between PH and kinase domains within AKT molecule. Consistently, AKT1-H89A/E91A mutant (zinc-binding-deficient) fails to respond to zinc ions and exhibits strong interaction between PH and kinase domains, and it is less oncogenic in orthotopic xenograft model of prostate cancer. On the other hand, the AKT1-W80L mutant with minimum intra-molecular interaction between PH and kinase domains shows strong tumor promoting capacity although it could not be further stimulated by zinc ions. Overall, this study reveals a distinctive regulatory mechanism of AKT activation and implies a tumor promoting role of the zinc ions in prostate cancer.</p>","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505256","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":"IL-17RA/CTSK axis mediates H. pylori-induced castration-resistant prostate cancer growth","authors":"Guowen Lin,&nbsp;Feng Tian,&nbsp;Qiwei Yu,&nbsp;Xiaoling Weng,&nbsp;Nanhui Yu,&nbsp;Feng Zhang,&nbsp;Chen Yi,&nbsp;Jian Ye,&nbsp;Dingwei Ye","doi":"10.1038/s41388-024-03169-z","DOIUrl":"10.1038/s41388-024-03169-z","url":null,"abstract":"In this investigation, we explored the molecular dynamics guiding the progression of castration-resistant prostate cancer (CRPC) influenced by Helicobacter pylori (H. pylori)-mediated M2 polarization of macrophages through the IL-17RA/CTSK/EMT axis. An 830-patient clinical trial categorized subjects into hormone-sensitive prostate cancer (HSPC) and CRPC groups. H. pylori infection, evaluated by ELISA, exhibited a higher incidence in CRPC patients, impacting overall survival (OS) and progression-free survival. In-depth in vitro and in vivo experiments, including 16S rDNA sequencing, immunohistochemical tests, and transcriptome analysis, unveiled that H. pylori promotes CRPC growth and metastasis by upregulating IL-17RA and CTSK, leading to enhanced EMT. Notably, M2 macrophages emerged as pivotal immune cells influencing CRPC progression. This study uncovers a novel pathway wherein H. pylori enrichment exacerbates CRPC by inducing macrophage M2 polarization, IL-17RA/CTSK expression, and EMT activation, shedding light on a previously unrecognized mechanism contributing to the growth and metastasis of CRPC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"43 49","pages":"3598-3616"},"PeriodicalIF":6.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471603","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}