Chen Guangyuan, Xie Jiabin, Huang Ping, Yang Zhihong
Department of Gynecology, Songgang People's Hospital, Shenzhen, Guangdong 518105, P.R. China.
Oncol Lett. 2016 Sep;12(3):1821-1825. doi: 10.3892/ol.2016.4829. Epub 2016 Jul 8.
The Hippo pathway is dysregulated in multiple types of human cancer, including ovarian cancer. Nuclear expression of yes-associated protein 1 (YAP1), a downstream transcription coactivator of the Hippo pathway, has been demonstrated to promote tumorigenesis in ovarian cancer and may serve as a poor prognostic indicator. However, transcriptional coactivator with PDZ binding motif (TAZ), a downstream target of the Hippo pathway and paralog of YAP in mammalian cells, has not been fully investigated in ovarian cancer. The present study aimed to investigate the dysregulation and biological function of TAZ in ovarian cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that TAZ mRNA and protein levels, respectively, were upregulated in ovarian cancer, and a meta-analysis of ovarian cancer microarray datasets identified that increased expression of TAZ mRNA is correlated with poor prognosis in patients with ovarian cancer. In addition, TAZ-knockdown in ovarian cancer cells demonstrated that TAZ regulates the migration, proliferation and epithelial-mesenchymal transition of ovarian cancer cells. Furthermore, pharmacological disruption of the YAP/TAZ/TEA domain protein complex resulted in a decrease in ovarian cancer cell migration, proliferation and vimentin expression. The results of the present study indicate that the overexpression of TAZ is important in the development and progression of ovarian cancer, and may function as a potential drug target for treatment of this disease entity.
Hippo信号通路在包括卵巢癌在内的多种人类癌症中存在失调。Yes相关蛋白1（YAP1）是Hippo信号通路的下游转录共激活因子，其核表达已被证明可促进卵巢癌的肿瘤发生，并且可能是预后不良的指标。然而，具有PDZ结合基序的转录共激活因子（TAZ）作为Hippo信号通路的下游靶点以及哺乳动物细胞中YAP的旁系同源物，在卵巢癌中尚未得到充分研究。本研究旨在探讨TAZ在卵巢癌中的失调情况及其生物学功能。逆转录-定量聚合酶链反应和蛋白质印迹分析显示，TAZ的mRNA和蛋白质水平在卵巢癌中均上调，对卵巢癌微阵列数据集的荟萃分析表明，TAZ mRNA表达增加与卵巢癌患者的预后不良相关。此外，在卵巢癌细胞中敲低TAZ表明，TAZ可调节卵巢癌细胞的迁移、增殖和上皮-间质转化。此外，YAP/TAZ/TEA结构域蛋白复合物的药理学破坏导致卵巢癌细胞迁移、增殖和波形蛋白表达减少。本研究结果表明，TAZ的过表达在卵巢癌的发生和发展中起重要作用，并且可能作为治疗该疾病实体的潜在药物靶点。
