Passaniti Antonino, Brusgard Jessica L, Qiao Yiting, Sudol Marius, Finch-Edmondson Megan
Department of Pathology and Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, and the Veterans Administration Health Service, Baltimore, MD, USA.
The Mechanobiology Institute (MBI) and the NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
Adv Exp Med Biol. 2017;962:435-448. doi: 10.1007/978-981-10-3233-2_26.
The Runt-domain (RD) transcription factors (RUNX genes) are an important family of transcriptional mediators that interact with a variety of proteins including the Hippo pathway effector proteins, YAP and TAZ. In this chapter we focus on two examples of RUNX-TAZ/YAP interactions that have particular significance in human cancer. Specifically, recent evidence has found that RUNX2 cooperates with TAZ to promote epithelial to mesenchymal transition mediated by the soluble N-terminal ectodomain of E-Cadherin, sE-Cad. Contrastingly, in gastric cancer, RUNX3 acts as a tumor suppressor via inhibition of the YAP-TEAD complex and disruption of downstream YAP-mediated gene transcription and the oncogenic phenotype. The reports highlighted in this chapter add to the growing repertoire of instances of Hippo pathway crosstalk that have been identified in cancer. Elucidation of these increasingly complex interactions may help to identify novel strategies to target Hippo pathway dysregulation in human cancer.
Runt结构域(RD)转录因子(RUNX基因)是一类重要的转录调节因子家族,可与多种蛋白质相互作用,包括Hippo信号通路效应蛋白YAP和TAZ。在本章中,我们重点关注RUNX与TAZ/YAP相互作用的两个例子,它们在人类癌症中具有特殊意义。具体而言,最近的证据发现,RUNX2与TAZ协同作用,促进由E-钙黏蛋白可溶性N端胞外域sE-Cad介导的上皮-间质转化。相反,在胃癌中,RUNX3通过抑制YAP-TEAD复合物以及破坏下游YAP介导的基因转录和致癌表型发挥肿瘤抑制作用。本章强调的这些报告增加了在癌症中已确定的Hippo信号通路串扰实例。阐明这些日益复杂的相互作用可能有助于确定针对人类癌症中Hippo信号通路失调的新策略。