1] Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. [2] Genes and Development Program, and Cancer Biology Program, Graduate School for Biological Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. [3] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
VIB Center for the Biology of Disease, KU Leuven Center for Human Genetics, University of Leuven 3000, Belgium.
Nat Rev Drug Discov. 2014 Jan;13(1):63-79. doi: 10.1038/nrd4161. Epub 2013 Dec 13.
The Hippo signalling pathway is an emerging growth control and tumour suppressor pathway that regulates cell proliferation and stem cell functions. Defects in Hippo signalling and hyperactivation of its downstream effectors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) contribute to the development of cancer, which suggests that pharmacological inhibition of YAP and TAZ activity may be an effective anticancer strategy. Conversely, YAP and TAZ can also have beneficial roles in stimulating tissue repair and regeneration following injury, so their activation may be therapeutically useful in these contexts. A complex network of intracellular and extracellular signalling pathways that modulate YAP and TAZ activities have recently been identified. Here, we review the regulation of the Hippo signalling pathway, its functions in normal homeostasis and disease, and recent progress in the identification of small-molecule pathway modulators.
Hippo 信号通路是一种新兴的生长调控和肿瘤抑制通路，它调节细胞增殖和干细胞功能。Hippo 信号通路的缺陷和其下游效应物 Yes 相关蛋白 (YAP) 和 PDZ 结合基序转录共激活因子 (TAZ) 的过度激活导致癌症的发生，这表明抑制 YAP 和 TAZ 的活性可能是一种有效的抗癌策略。相反，YAP 和 TAZ 在损伤后刺激组织修复和再生方面也具有有益作用，因此在这些情况下激活它们可能具有治疗意义。最近发现了一个调节 YAP 和 TAZ 活性的细胞内和细胞外信号通路的复杂网络。在这里，我们综述了 Hippo 信号通路的调控、它在正常动态平衡和疾病中的功能，以及最近在鉴定小分子通路调节剂方面的进展。
