title: G protein-coupled receptors: bridging the gap from the extracellular signals to the Hippo pathway.
abstract: The Hippo pathway is crucial in organ size control, whereas its dysregulation contributes to organ degeneration or tumorigenesis. The kinase cascade of MST1/2 and LATS1/2 and the coupling transcription co-activators YAP/TAZ represent the core components of the Hippo pathway. Extensive studies have identified a number of upstream regulators of the Hippo pathway, including contact inhibition, mechanic stress, extracellular matrix stiffness, cytoskeletal rearrangement, and some molecules of cell polarity and cell junction. However, how the diffuse extracellular signals regulate the Hippo pathway puzzles the researchers for a long time. Unexpectedly, recent elegant studies demonstrated that stimulation of some G protein-coupled receptors (GPCRs), such as lysophosphatidic acid receptor, sphingosine-1-phosphate receptor, and the protease activated receptor PAR1, causes potent YAP/TAZ dephosphorylation and activation by promoting actin cytoskeleton assemble. In this review, we briefly describe the components of the Hippo pathway and focus on the recent progress with respect to the regulation of the Hippo pathway by GPCRs and G proteins in cancer cells. In addition, we also discuss the potential therapeutic roles targeting the Hippo pathway in human cancers.
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China School of Life Science, Fudan University, Shanghai 200433, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China Department of Biological Sciences, Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China qlei@fudan.edu.cn.
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Lei
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D049109:Cell Proliferation / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D000090683:Hippo Signaling Pathway; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009929:Organ Size / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D043562:Receptors, G-Protein-Coupled; D017346:Protein Serine-Threonine Kinases
keywords: G proteins; GPCR; Hippo; TAZ; YAP; cancer