The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment.

The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment.
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DOI:
10.1038/nrd4161
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发表时间:
2014-01
期刊:
Nature reviews. Drug discovery
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其他
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Hippo信号通路是一种新兴的生长控制和肿瘤抑制通路,调节细胞增殖和干细胞功能。Hippo信号传导的缺陷及其下游效应物雅普和TAZ的超活化有助于癌症的发展,这表明药理学抑制雅普和TAZ活性可能是有效的抗癌策略。相反,雅普和TAZ也可以在刺激损伤后的组织修复和再生中发挥有益的作用,因此雅普和TAZ的活化在这些情况下可能是有用的。最近,人们发现了一种调节雅普和TAZ活性的细胞内和细胞外信号通路的复杂网络。本文综述了Hippo信号通路的调控、在正常稳态和疾病中的作用以及小分子信号通路调节剂的研究进展。
The Hippo signaling pathway is an emerging growth control and tumor suppressor pathway that regulates cell proliferation and stem cell functions. Defects in Hippo signaling and hyperactivation of its downstream effectors YAP and TAZ contribute to the development of cancer, suggesting that pharmacological inhibition of YAP and TAZ activity may be an effective anticancer strategy. Conversely, YAP and TAZ can also play beneficial roles in stimulating tissue repair and regeneration following injury, therefore activation of YAP and TAZ may be useful in these contexts. Recently, a complex network of intracellular and extracellular signaling pathways that modulate YAP and TAZ activities have been identified. Here we review the regulation of the Hippo signaling pathway, its functions in normal homeostasis and disease, and recent progress in the identification of small molecule pathway modulators.
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