The Hippo-YAP signaling pathway and contact inhibition of growth
The Hippo-YAP signaling pathway and contact inhibition of growth
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DOI：
10.1242/jcs.140103
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发表时间：
2014-02-15
影响因子：
4
通讯作者：
Kim, Nam-Gyun
中科院分区：
文献类型：
--
作者：
Gumbiner, Barry M.;Kim, Nam-Gyun
Hippo-YAP通路通过接触抑制以及组织中细胞物理状态的其他属性介导细胞增殖的控制。几种机制感知细胞的空间和物理组织，并通过不同的上游模块发挥作用来刺激希波- yap信号传导：粘附连接或cadherin-catenin复合物，上皮极性和紧密连接复合物，FAT-Dachsous形态因子途径，以及细胞形状，肌动球蛋白或机械转导。可溶性细胞外因子也调节Hippo通路信号，通常抑制其活性。事实上，Hippo通路介导了接触抑制和有丝分裂信号传导之间的相互关系。因此，在集落边缘、组织伤口或肿瘤上的细胞对环境水平的生长因子更敏感，更有可能通过YAP和/或taz依赖的过程增殖、迁移或分化。因此，Hippo-YAP通路感知并响应组织中细胞的物理组织，并与经典的生长因子介导的信号通路协调这些物理线索。本文主要关注Hippo-YAP信号的生物学意义，以及该通路的上游调控模块如何相互作用以产生生物学结果。
The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherin-catenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZ-dependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factor-mediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes.