Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc, 77900 Olomouc, Czech Republic.
Int J Mol Sci. 2021 Dec 31;23(1):430. doi: 10.3390/ijms23010430.
The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways' role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.
Yes 相关蛋白(YAP)和与 PDZ 结合基序的转录共激活因子(TAZ)是转录共激活因子,是 Hippo 信号通路的成员,在细胞生长调控、胚胎发育、再生、增殖以及癌症起源和进展中发挥关键作用。其机制涉及未磷酸化的 YAP/TAZ 复合物与抑制物的核结合,从而将转录增强相关结构域(TEAD)从其抑制物中释放出来。该活性三元复合物负责上述生物学效应。已有报道称,YAP/TAZ 在癌症干细胞和肿瘤耐药中过表达。这种耐药性涉及化疗、靶向治疗和免疫治疗。本综述概述了 YAP/TAZ 通路在致癌作用和肿瘤微环境中的作用。还讨论了潜在的治疗替代方案。