Physiological and pathological roles of the Hippo-YAP/TAZ signaling pathway in liver formation, homeostasis, and tumorigenesis.
Physiological and pathological roles of the Hippo-YAP/TAZ signaling pathway in liver formation, homeostasis, and tumorigenesis.
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Hippo-YAP/TAZ信号通路在肝脏形成、稳态和肿瘤发生中的生理和病理作用
作者：
肝脏在新陈代谢和解毒中起着中心的稳态作用，并且具有从其不断暴露的各种损伤引起的损伤中完全恢复的显著能力。为了实现这些功能，肝脏必须保持特定的大小，因此必须调节其细胞数量。它还必须去除损害肝功能并可能导致肝硬化和肝癌等疾病的衰老，转化和/或损伤细胞。尽管它们的重要性，然而，机制管理肝脏大小控制和体内平衡抵制描绘。Hippo细胞内信号通路及其下游效应子--转录共激活因子Yes‐相关蛋白（雅普）和具有PDZ‐结合基序的转录共激活因子（TAZ）的发现为这些机制提供了部分解释。Hippo雅普/TAZ通路被认为是细胞对其直接微环境及其周围细胞的传感器，因为该通路响应于诸如ECM、细胞-细胞张力和细胞粘附等元素的变化。一旦被触发，Hippo信号传导负调节雅普/TAZ与转录因子如TEAD和Smad的结合，控制它们驱动细胞应答如增殖、存活和干性所需的基因表达的能力。已经产生了许多缺乏雅普/TAZ的KO小鼠品系，以及显示雅普/TAZ超活化的转基因小鼠，并且已经报道了这些突变对肝脏发育、大小、再生、稳态和肿瘤发生的影响。本文综述了Hippo雅普/TAZ信号通路的组成和调控，并结合肝脏的生理和病理对该通路进行了讨论。Hippo雅普/TAZ通路被认为是细胞对其直接微环境及其周围细胞的传感器，因为该通路响应于诸如ECM、细胞-细胞张力和细胞粘附等元素的变化。
The liver plays central homeostatic roles in metabolism and detoxification, and has a remarkable capacity to fully recover from injuries caused by the various insults to which it is constantly exposed. To fulfill these functions, the liver must maintain a specific size and so must regulate its cell numbers. It must also remove senescent, transformed, and/or injured cells that impair liver function and can lead to diseases such as cirrhosis and liver cancer. Despite their importance, however, the mechanisms governing liver size control and homeostasis have resisted delineation. The discovery of the Hippo intracellular signaling pathway and its downstream effectors, the transcriptional coactivators Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ), has provided partial elucidation of these mechanisms. The Hippo‐YAP/TAZ pathway is considered to be a cell’s sensor of its immediate microenvironment and the cells that surround it, in that this pathway responds to changes in elements such as the ECM, cell–cell tension, and cell adhesion. Once triggered, Hippo signaling negatively regulates the binding of YAP/TAZ to transcription factors such as TEAD and Smad, controlling their ability to drive gene expression needed for cellular responses such as proliferation, survival, and stemness. Numerous KO mouse strains lacking YAP/TAZ, as well as transgenic mice showing YAP/TAZ hyperactivation, have been generated, and the effects of these mutations on liver development, size, regeneration, homeostasis, and tumorigenesis have been reported. In this review, I summarize the components and regulation of Hippo‐YAP/TAZ signaling, and discuss this pathway in the context of liver physiology and pathology. The Hippo‐YAP/TAZ pathway is considered to be a cell’s sensor of its immediate microenvironment and the cells that surround it, in that this pathway responds to changes in elements such as the ECM, cell–cell tension, and cell adhesion.
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影响因子：
10.5
作者：
Chen Q;Zhang N;Xie R;Wang W;Cai J;Choi KS;David KK;Huang B;Yabuta N;Nojima H;Anders RA;Pan D
通讯作者：
Pan D
Hippo 通路中血管动蛋白结合诱导的 Merlin/NF2 激活
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
12.8
作者：
Lu L;Finegold MJ;Johnson RL
通讯作者：
Johnson RL
影响因子：
64.8
作者：
Claveria, Cristina;Giovinazzo, Giovanna;Torres, Miguel
通讯作者：
Torres, Miguel
DOI：
10.1073/pnas.0605266104
发表时间：
2007-01-30
影响因子：
11.1
作者：
Hossain, Zakir;Ali, Safiah Mohamed;Hunziker, Walter
通讯作者：
Hunziker, Walter