Hippo信号通路在乳腺癌中的调控机制及作用

摘要

Hippo信号通路是调控器官大小和肿瘤发生发展的关键通路,近年来受到广泛的关注.TAZ/YAP作为哺乳动物中Hippo信号通路两个核心下游效应分子,通过Hippo信号通路依赖性和非依赖性的机制受到细胞内外信号的严密调控.除了参与正常乳腺组织发育,Hippo信号通路还在人乳腺癌细胞的增殖、分化、凋亡、迁移、侵袭、上皮-间质转化和干性维持等多个过程中起着关键性作用.本文总结了Hippo信号通路的调控机制和调节信号,阐述了Hippo信号通路异常在乳腺癌发生发展中的作用,并讨论了其在乳腺癌中作为治疗靶点的临床策略.%Hippo signaling pathway has attracted broad attention due to its essential roles in controlling organ size and tumorigenesis.TAZ/YAP,two core downstream molecules of the Hippo signaling pathway in mammals,are tightly regulated by a wide range of extracellular and intrinsic signals in both Hippo signaling pathway-dependent and -independent manners.Besides their roles in the development and function of normal mammary glands,TAZ/YAP display remarkable potency and relevance to multiple aspects of human breast carcinogenesis,including cellular proliferation,differentiation,apoptosis,migration,invasion,epithelial-mesenchymal transition and stemness.In this review,we summarize the regulators of TAZ/YAP,discuss the significant contribution of the Hippo signaling pathway to human breast cancers and highlight their potential therapeutic roles.