title: The Hippo-YAP signaling pathway and contact inhibition of growth.
abstract: The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherin-catenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZ-dependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factor-mediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes.
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Gumbiner
authors.forename: Nam-Gyun
authors.initials: NG
authors.lastname: Kim
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D018797:Cell Cycle Proteins; D016764:Cell Polarity; D049109:Cell Proliferation; D000090683:Hippo Signaling Pathway; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Cadherin; Hippo; Mechanotransduction; Mitogenesis; Polarity; YAP