脑海绵状血管畸形1决定前列腺癌细胞中YAP/TAZ信号依赖的转移特征。

Cerebral Cavernous Malformation 1 Determines YAP/TAZ Signaling-Dependent Metastatic Hallmarks of Prostate Cancer Cells.

作者信息

Park Sangryong, Lee Ho-Young, Kim Jayoung, Park Hansol, Ju Young Seok, Kim Eung-Gook, Kim Jaehong

机构信息

Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Korea.

Department of Health Sciences and Technology, Gachon Advanced Institute for Health Science and Technology, Gachon University, Incheon 21999, Korea.

出版信息

Cancers (Basel). 2021 Mar 5;13(5):1125. doi: 10.3390/cancers13051125.

DOI:10.3390/cancers13051125

PMID:33807895

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7961486/

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 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. We also 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 suppression of YAP/TAZ signaling, indicating that CCM1 and DDX5 are novel upstream regulators of YAP/TAZ signaling. Our findings highlight the importance of CCM1-DDX5-YAP/TAZ signaling in the metastasis of prostate cancer cells.

摘要

增强型Yes相关蛋白（YAP）/含PDZ结合基序的转录共激活因子（TAZ）信号传导与前列腺癌的前列腺外扩展相关。然而，YAP/TAZ信号传导变得过度活跃并驱动前列腺癌进展的机制目前尚不清楚。在本研究中，我们发现CCM1在晚期前列腺癌中特异性高表达，且与前列腺癌患者的无转移生存期和总生存期呈负相关。我们还证明，CCM1通过调节YAP/TAZ信号传导诱导多种类型前列腺癌细胞的转移。从机制上讲，CCM1是一种在脑海绵状血管畸形中发生突变的基因，它抑制DDX5，而DDX5调节YAP/TAZ信号传导的抑制，这表明CCM1和DDX5是YAP/TAZ信号传导的新型上游调节因子。我们的研究结果突出了CCM1-DDX5-YAP/TAZ信号传导在前列腺癌细胞转移中的重要性。