Dong Xiaoming, Meng Lingbin, Liu Pinyi, Ji Rui, Su Xuling, Xin Ying, Jiang Xin
Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, People's Republic of China.
Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, People's Republic of China.
Cancer Manag Res. 2019 Jul 8;11:6245-6252. doi: 10.2147/CMAR.S197921. eCollection 2019.
Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two homologous transcriptional coactivators and the final effectors of the Hippo signaling transduction pathway. The transcriptional activity of YAP/TAZ is dependent on their recruitment to the nucleus, which promotes binding to the transcription factor of TEA domain family members 1-4 (TEAD1-4). In Hippo-signaling pathway, YAP/TAZ is inactivated and its translocation to the nucleus is blocked via a core kinase cascade stimulated by a variety of upstream signals, such as G-protein-coupled receptor signaling, mechanical pressure, and adherens junction signaling. This pathway plays a very important role in regulating organ size, tissue homeostasis, and tumor development. In recent years, many studies have reported upregulation or nuclear localization of YAP/TAZ in a number of human malignancies, such as breast cancer, melanoma, lung cancer, especially squamous cell carcinoma in different organs. A large number of experiments demonstrate that YAP/TAZ activation promotes cancer formation, progression, and metastasis. Therefore, in this review, we summarize the evidence of regulation and function of YAP/TAZ and discuss its role in squamous cell carcinoma. Collectively, this summary strongly suggests that targeting aberrant YAP/TAZ activation is a promising strategy for the suppression of squamous cell carcinoma.
Yes相关蛋白(YAP)和具有PDZ结合基序的转录共激活因子(TAZ)是两种同源的转录共激活因子,也是Hippo信号转导通路的最终效应分子。YAP/TAZ的转录活性取决于它们被募集到细胞核,这促进了与TEA结构域家族成员1-4(TEAD1-4)转录因子的结合。在Hippo信号通路中,YAP/TAZ失活,并且其向细胞核的转运通过由多种上游信号(如G蛋白偶联受体信号、机械压力和黏附连接信号)刺激的核心激酶级联反应而被阻断。该通路在调节器官大小、组织稳态和肿瘤发展中起着非常重要的作用。近年来,许多研究报道了YAP/TAZ在多种人类恶性肿瘤中上调或核定位,如乳腺癌、黑色素瘤、肺癌,尤其是不同器官的鳞状细胞癌。大量实验表明,YAP/TAZ激活促进癌症形成、进展和转移。因此,在本综述中,我们总结了YAP/TAZ调节和功能的证据,并讨论了其在鳞状细胞癌中的作用。总的来说,这一总结强烈表明,靶向异常的YAP/TAZ激活是抑制鳞状细胞癌的一种有前景的策略。