{"title":"USP24 promotes hepatocellular carcinoma progression by deubiquitinating and stabilizing YAP1.","authors":"Huizhuang Shan, Jiaguo Yuan, Luhua Xian, Wenmin Li, Yanfen Ge, Lei Zhang, Ting Lin, Mingwei Lan, Junru Liu, Yanfei Luo, Yingli Wu, Xinhua Xiao","doi":"10.1186/s12935-025-03796-w","DOIUrl":null,"url":null,"abstract":"<p><p>Yes-associated protein 1 (YAP1) plays a pivotal role in promoting the progression of hepatocellular carcinoma (HCC). Emerging evidence shows that inducing YAP1 degradation represents a promising strategy. Here, we identified USP24 as a bona fide deubiquitinating enzyme for YAP1. USP24 directly interacts with and deubiquitinates YAP1, thereby stabilizing YAP1 protein levels. Clinically, USP24 was significantly upregulated in HCC tissues and correlated with poor patient prognosis. Depletion of USP24 significantly suppressed the proliferation of HCC cells in vitro, which could be rescued by restoration of YAP1. Consistent with these findings, USP24 knockdown inhibited tumor growth in a xenograft mouse model. Overall, our study reveals that the USP24/YAP1 axis plays a critical role in the malignant progression of HCC, thus providing rationale for potential therapeutic interventions for YAP1-driven HCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"164"},"PeriodicalIF":5.3000,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034148/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03796-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Yes-associated protein 1 (YAP1) plays a pivotal role in promoting the progression of hepatocellular carcinoma (HCC). Emerging evidence shows that inducing YAP1 degradation represents a promising strategy. Here, we identified USP24 as a bona fide deubiquitinating enzyme for YAP1. USP24 directly interacts with and deubiquitinates YAP1, thereby stabilizing YAP1 protein levels. Clinically, USP24 was significantly upregulated in HCC tissues and correlated with poor patient prognosis. Depletion of USP24 significantly suppressed the proliferation of HCC cells in vitro, which could be rescued by restoration of YAP1. Consistent with these findings, USP24 knockdown inhibited tumor growth in a xenograft mouse model. Overall, our study reveals that the USP24/YAP1 axis plays a critical role in the malignant progression of HCC, thus providing rationale for potential therapeutic interventions for YAP1-driven HCC.
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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