Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA; Seattle Tumor Translational Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Dev Biol. 2021 Jul;475:205-221. doi: 10.1016/j.ydbio.2020.12.018. Epub 2021 Jan 8.
YAP1 is a transcriptional co-activator whose activity is controlled by the Hippo signaling pathway. In addition to important functions in normal tissue homeostasis and regeneration, YAP1 has also prominent functions in cancer initiation, aggressiveness, metastasis, and therapy resistance. In this review we are discussing the molecular functions of YAP1 and its roles in cancer, with a focus on the different mechanisms of de-regulation of YAP1 activity in human cancers, including inactivation of upstream Hippo pathway tumor suppressors, regulation by intersecting pathways, miRNAs, and viral oncogenes. We are also discussing new findings on the function and biology of the recently identified family of YAP1 gene fusions, that constitute a new type of activating mutation of YAP1 and that are the likely oncogenic drivers in several subtypes of human cancers. Lastly, we also discuss different strategies of therapeutic inhibition of YAP1 functions.
YAP1 是转录共激活因子，其活性受 Hippo 信号通路的调控。除了在正常组织稳态和再生中具有重要功能外，YAP1 在癌症的起始、侵袭性、转移和治疗耐药性方面也具有突出的功能。在这篇综述中，我们讨论了 YAP1 的分子功能及其在癌症中的作用，重点讨论了人类癌症中 YAP1 活性失调的不同机制，包括上游 Hippo 通路肿瘤抑制因子的失活、相交途径、miRNAs 和病毒癌基因的调节。我们还讨论了最近发现的 YAP1 基因融合家族的功能和生物学的新发现，该家族构成了 YAP1 的一种新型激活突变，并且可能是几种人类癌症亚型的致癌驱动因素。最后，我们还讨论了抑制 YAP1 功能的不同治疗策略。
