The Hippo pathway in disease and therapy: cancer and beyond.
The Hippo pathway in disease and therapy: cancer and beyond.
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DOI：
10.1186/2001-1326-3-22
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发表时间：
2014
影响因子：
10.6
通讯作者：
Hergovich A
中科院分区：
文献类型：
--
作者：
Gomez M;Gomez V;Hergovich A
Hippo肿瘤抑制途径协调细胞增殖、细胞死亡和细胞分化以调节组织生长控制。在哺乳动物中，保守的核心Hippo信号传导模块在不同水平上接收信号输入，以确保作为转录共激活因子的雅普/TAZ活性的适当调节。虽然核心模块成员MST 1/2、萨尔瓦多、LATS 1/2和MOB 1被认为具有肿瘤抑制功能，但雅普/TAZ主要被描述为具有致癌作用，尽管一些报告提供了支持雅普/TAZ在某些癌症环境中的生长抑制作用的证据。有趣的是，哺乳动物Hippo信号传导也与非癌症疾病有关，并在损伤后的组织再生中发挥作用。这些发现累积表明，根据疾病背景，可能需要对Hippo通路进行药理学抑制或激活。在这篇综述中，我们首先总结了哺乳动物Hippo通路在肿瘤形成中的功能，然后讨论了涉及Hippo信号核心成分的非癌症疾病，特别关注我们目前对MST 1/2和雅普/TAZ的非癌症作用的理解。此外，可能的药理学干预与河马信号的利弊将审查，特别强调抗癌药物的开发和再生医学。
The Hippo tumour suppressor pathway co-ordinates cell proliferation, cell death and cell differentiation to regulate tissue growth control. In mammals, a conserved core Hippo signalling module receives signal inputs on different levels to ensure the proper regulation of YAP/TAZ activities as transcriptional co-activators. While the core module members MST1/2, Salvador, LATS1/2 and MOB1 have been attributed tumour suppressive functions, YAP/TAZ have been mainly described to have oncogenic roles, although some reports provided evidence supporting growth suppressive roles of YAP/TAZ in certain cancer settings. Intriguingly, mammalian Hippo signalling is also implicated in non-cancer diseases and plays a role in tissue regeneration following injury. Cumulatively, these findings indicate that the pharmacological inhibition or activation of the Hippo pathway could be desirable depending on the disease context. In this review, we first summarise the functions of the mammalian Hippo pathway in tumour formation, and then discuss non-cancer diseases involving Hippo signalling core components with a specific focus on our current understanding of the non-cancer roles of MST1/2 and YAP/TAZ. In addition, the pros and cons of possible pharmacological interventions with Hippo signalling will be reviewed, with particular emphasis on anti-cancer drug development and regenerative medicine.