Cerebral cavernous malformation 1 determines YAP/TAZ signaling dependent metastatic hallmarks of prostate cancer cells
Cerebral cavernous malformation 1 determines YAP/TAZ signaling dependent metastatic hallmarks of prostate cancer cells
Abstract Enhanced Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling is correlated with the extraprostatic extension of prostate cancer. However, the mechanism by which YAP/TAZ signaling becomes hyperactive and drives prostate cancer progression is currently unclear. In this study, we demonstrated that CCM1 induces the metastasis of multiple types of prostate cancer cells by regulating YAP/TAZ signaling. Mechanistically, CCM1, a gene mutated in cerebral cavernous malformation, suppresses DDX5, which regulates the PLK1-mediated suppression of YAP/TAZ signaling, indicating that CCM1 and DDX5 are novel upstream regulators of YAP/TAZ signaling. We also revealed that higher expression of CCM1, which is uniquely found in advanced prostate cancer, is inversely correlated with metastasis-free and overall survival in patients with prostate cancer. Our findings highlight the importance of CCM1-DDX5-PLK1-YAP/TAZ signaling in the metastasis of prostate cancer cells. Statement of SignificanceOur analysis of CCM1 expression and function represents a candidate predictive biomarker for prostate cancer metastasis and provides an evidence that abnormality of CCM1 can be pathogenic in prostate cancer. Importantly, CCM1 regulation of metastasis progression appears to a common molecular event in metastatic prostate cancer cells arising in disparate genetic backgrounds.
Park Sangryoung、Lee Ho-Yong、Kim Jayoung、Ju Young Seok、Park Hansol、Kim Eung-Gook、Kim Jaehong
Department of Biochemistry, College of Medicine, Gachon UniversityDepartment of Biochemistry, College of Medicine, Gachon University||Department of Health Sciences and Technology, Gachon Advanced Institute for Health Science and Technology, Gachon UniversityDivision of Cancer Biology and Therapeutics, Departments of Surgery & Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterBiomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology||Graduate School of Medical Science and Engineering,, Korea Advanced Institute of Science and TechnologyBiomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and TechnologyDepartment of Biochemistry, Chungbuk National University College of MedicineDepartment of Biochemistry, College of Medicine, Gachon University||Department of Health Sciences and Technology, Gachon Advanced Institute for Health Science and Technology, Gachon University
肿瘤学基础医学分子生物学
Cerebral cavernous malformationprostate cancermetastasisYAP/TAZ signaling
Park Sangryoung,Lee Ho-Yong,Kim Jayoung,Ju Young Seok,Park Hansol,Kim Eung-Gook,Kim Jaehong.Cerebral cavernous malformation 1 determines YAP/TAZ signaling dependent metastatic hallmarks of prostate cancer cells[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.04.23.057778.点此复制
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