学术报告
题目：The Hippo Pathway: Regulation and Implications in Cancer
报告人：Faxing Yu
Department of Pharmacology and Moores Cancer Center, University of California San Diego
时间：2014年1月10日（周五）下午13:00 PM
地点：清华大学生命科学馆143室
The Hippo pathway is crucial in animal development and tissue homeostasis by regulating cell proliferation, death, and differentiation. However, upstream signals that regulate the mammalian Hippo pathway have remained elusive until recently. In this talk, I will discuss the regulation of the Hippo pathway by G-protein-coupled receptor (GPCR) signaling. Serum-borne lysophosphatidic acid (LPA) and sphingosine 1-phosphophate (S1P) act through G12/13-coupled receptors to inhibit the Hippo pathway kinases Lats1/2, thereby activating YAP/TAZ transcription coactivators. Furthermore, activation of YAP/TAZ is involved in LPA-induced gene expression, cell migration, and proliferation. In contrast, stimulation of Gs-coupled receptors by glucagon or epinephrine activates Lats1/2 kinase activity, thereby inhibiting YAP/TAZ function. Thus, GPCR signaling can either activate or inhibit the Hippo-YAP pathway depending on the coupled G protein. Dysregulations of GPCR signaling frequently occur in human cancers; for instance, an activating mutation of Gq or G11 is present in approximately 80% uveal melanomas (UM) -- the most common cancer of the eye in adults. These mutant Gq and G11 are able to stimulate YAP/TAZ activity, and YAP/TAZ are potently activated in UM cell lines and UM clinical specimens with Gq/11 mutation. The hyperactivation of YAP/TAZ by dysregulated GPCR signaling may contribute to development of UM and other types of human cancers.
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