YAP参与调控细胞上皮-间充质转化的研究进展

The Advance of YAP Regulating Epithelial-mesenchymal Transition in Cells

上皮-间充质转化(epithelial-mesenchymal transition,EMT)是上皮来源细胞在各种理化因素作用下经历表型转化获得间充质样细胞表型的过程.研究表明,有多种信号分子参与EMT的发生,并在胚胎发育、器官损伤修复和肿瘤的发生发展过程中起着关键作用.Yes相关蛋白(yes-associated protein,YAP)作为Hippo信号通路的下游效应分子,被广泛报道参与EMT的进程,调控多种基因的表达,起到调节细胞增殖、凋亡、器官发育和修复等作用.最新研究表明,YAP活性的变化直接介导肿瘤细胞的迁移和侵袭等能力的变化,而这些变化都伴随着EMT的发生.因此,YAP蛋白跟EMT的发生密切相关.本文就近年来关于YAP调控组织发育、器官纤维化及在肿瘤发生发展中的作用,以及相关分子机制的研究进行综述,并将阐明其与EMT之间的相互关系,以期为EMT的研究提供新的视角,进而为相关疾病的治疗提供新的分子靶点和诊断治疗策略.

Epithelial-mesenchymal transition（EMT） is a process by which epithelial-derived cells experience phenotypic transformation, gain mesenchymal-like cell phenotype under the condition of various physical and chemical factors. Many signaling molecules participate in regulating EMT during the process of embryo development, organ regeneration and tumor development. As the downstream effector of Hippo signal pathway, the role of YAP in EMT has been widely studied. It plays a dominant role in gene expression to control the cell proliferation and apoptosis, and organ development and regeneration. In addition, increasing evidences demonstrate that activity of YAP is closely related to tumor migration and invasion, along with the occurrence of EMT. Here, we reviewed the roles of YAP in EMT in tissue development, organ fibrosis and tumor development,and the progress of related molecular mechanisms, which is expected to broaden a new prospective for EMT studies and provide new molecular targets and diagnostic strategies for the treatment of related diseases.