Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Int J Mol Sci. 2019 Mar 29;20(7):1576. doi: 10.3390/ijms20071576.
The essential role of Hippo signaling pathway in cancer development has been elucidated by recent studies. In the gastrointestinal tissues, deregulation of the Hippo pathway is one of the most important driving events for tumorigenesis. It is widely known that Yes-associated protein 1 (YAP1) and WW domain that contain transcription regulator 1 (TAZ), two transcriptional co-activators with a PDZ-binding motif, function as critical effectors negatively regulated by the Hippo pathway. Previous studies indicate the involvement of YAP1/TAZ in mechanotransduction by crosstalking with the extracellular matrix (ECM) and the F-actin cytoskeleton associated signaling network. In gastric cancer (GC), YAP1/TAZ functions as an oncogene and transcriptionally promotes tumor formation by cooperating with TEAD transcription factors. Apart from the classic role of Hippo-YAP1 cascade, in this review, we summarize the current investigations to highlight the prominent role of YAP1/TAZ as a mechanical sensor and responder under mechanical stress and address its potential prognostic and therapeutic value in GC.
Hippo 信号通路在癌症发展中的重要作用已被最近的研究阐明。在胃肠道组织中,Hippo 通路的失调是肿瘤发生的最重要驱动事件之一。众所周知,Yes 相关蛋白 1(YAP1)和 WW 结构域包含转录调节剂 1(TAZ),这两个转录共激活因子具有 PDZ 结合基序,作为受 Hippo 通路负调控的关键效应因子发挥作用。先前的研究表明,YAP1/TAZ 通过与细胞外基质(ECM)和与 F-肌动蛋白细胞骨架相关的信号网络的交联参与机械转导。在胃癌(GC)中,YAP1/TAZ 作为癌基因发挥作用,并通过与 TEAD 转录因子合作转录促进肿瘤形成。除了 Hippo-YAP1 级联的经典作用外,在本综述中,我们总结了目前的研究进展,以强调 YAP1/TAZ 作为机械应激下机械传感器和响应者的突出作用,并探讨其在 GC 中的潜在预后和治疗价值。