He Zhengjin, Li Ruihan, Jiang Hai
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Front Cell Dev Biol. 2021 Jun 3;9:661718. doi: 10.3389/fcell.2021.661718. eCollection 2021.
The Hippo pathway is highly conserved from to mammals. As a key regulator of cell proliferation, the Hippo pathway controls tissue homeostasis and has a major impact on tumorigenesis. The originally defined core components of the Hippo pathway in mammals include STK3/4, LATS1/2, YAP1/TAZ, TEAD, VGLL4, and NF2. However, for most of these genes, mutations and copy number variations are relatively uncommon in human cancer. Several other recently identified upstream and downstream regulators of Hippo signaling, including FAT1, SHANK2, Gq/11, and SWI/SNF complex, are more commonly dysregulated in human cancer at the genomic level. This review will discuss major genomic events in human cancer that enable cancer cells to escape the tumor-suppressive effects of Hippo signaling.
从果蝇到哺乳动物，Hippo信号通路高度保守。作为细胞增殖的关键调节因子，Hippo信号通路控制组织稳态，并对肿瘤发生产生重大影响。哺乳动物中最初定义的Hippo信号通路的核心成分包括STK3/4、LATS1/2、YAP1/TAZ、TEAD、VGLL4和NF2。然而，对于这些基因中的大多数而言，突变和拷贝数变异在人类癌症中相对不常见。其他几个最近确定的Hippo信号上游和下游调节因子，包括FAT1、SHANK2、Gq/11和SWI/SNF复合物，在人类癌症的基因组水平上更常发生失调。本综述将讨论人类癌症中的主要基因组事件，这些事件使癌细胞能够逃避Hippo信号的肿瘤抑制作用。
