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 是一种转录共激活因子，其活性受 Hippo 信号通路控制。除了在正常组织稳态和再生中发挥重要作用外，YAP1还在癌症发生、侵袭、转移和治疗抵抗中发挥着重要作用。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，重点关注人类癌症中 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、交叉通路的调节、miRNA和病毒癌基因。我们还在讨论最近确定的 YAP1 基因融合家族的功能和生物学的新发现，它构成了 YAP1 的一种新型激活突变，并且可能是人类癌症几种亚型的致癌驱动因素。最后，我们还讨论了治疗性抑制 YAP1 功能的不同策略。