Hippo/YAP和Wnt/β-catenin通路的对话
收稿日期: 2013-08-26
修回日期: 2013-11-25
网络出版日期: 2014-01-25
基金资助
高等学校博士学科点专项科研基金(新教师类课题)(编号：20110071120033)资助
Crosstalk of Hippo/YAP and Wnt/β-catenin pathways
Received date: 2013-08-26
Revised date: 2013-11-25
Online published: 2014-01-25
Hippo/YAP通路和Wnt/β-catenin通路是在细胞的生长分化、组织器官形成以及成体干细胞的维持等方面都起着重要作用的两条信号通路。在哺乳动物细胞中, Wnt/β-catenin通路通过一系列胞质蛋白的相互作用, 使β-catenin蛋白在胞质内累积, 进而入核传递生长刺激信号。Hippo/YAP通路通过激酶级联反应磷酸化YAP/TAZ, 使其滞留在细胞质中, 抑制了YAP/TAZ的转录活性, 从而限制细胞的生长增殖, 诱导细胞凋亡。这两条通路的异常调控往往会导致肿瘤的发生。近年来越来越多的研究证实, Hippo/YAP 和Wnt/β-catenin在很多方面相互影响, 共同参与组织生长和胚胎发育的调控。研究这两个通路在肿瘤发生过程中的转导和调控以及它们相互作用的机制, 有助于为肿瘤的防治提供新的思路与策略。文章对这两条通路的协同作用及其分子机制进行了综述。
关键词： Hippo/YAP通路; Wnt/β-catenin通路; 交互作用; 肿瘤
许飞, 张进, 马端 . Hippo/YAP和Wnt/β-catenin通路的对话[J]. 遗传, 2014 , 36(2) : 95 -102 . DOI: 10.3724/SP.J.1005.2014.0095
Wnt/β-catenin and Hippo/YAP pathways are known to be important for development, growth, organogenesis, and maintenance of adult stem cells. In mammalian cells, Wnt signalling stabilises cytoplasmic β-catenin through several core molecules to promote β-catenin to enter the nucleus, thus delivers the growth -promoting signal. Hippo kinase cascade pathway promotes cytoplasmic localization of YAP/TAZ, which restricts cell proliferation and induces apoptosis. Deregula-tion of these two pathways could lead to tumorigenesis. Growing data indicate that these two pathways influence each other in a number of ways to properly regulate tissue growth and repair. Elucidating the regulatory mechanism and biological functions of Hippo/YAP and Wnt/β-catenin pathways might reveal potential targets for tumor therapeutic intervention. In this review, we discuss on the interactions between Wnt/β-catenin and Hippo/YAP pathways, and how these interactions contribute to tumorigenesis.
Key words： Hippo/YAP pathway; Wnt/β-catenin pathway; interaction; cancer
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