title: RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer.
abstract: The establishment and maintenance of epithelial polarity must be correctly controlled for normal development and homeostasis. Tight junctions (TJ) in vertebrates define apical and basolateral membrane domains in polarized epithelia via bi-directional, complex signalling pathways between TJ themselves and the cytoskeleton they are associated with. RhoGTPases are central to these processes and evidence suggests that their regulation is coordinated by interactions between GEFs and GAPs with junctional, cytoplasmic adapter proteins. In this InFocus review we determine that the expression, localization or stability of a variety of these adaptor proteins is altered in various cancers, potentially representing an important mechanistic link between loss of polarity and cancer. We focus here, on two well characterized RhoGTPases Cdc42 and RhoA who's GEFs and GAPs are predominantly localized to TJ via cytoplasmic adaptor proteins.
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1 V 9EL, UK. Electronic address: c.zihni@ucl.ac.uk.
authors.forename: Ceniz
authors.initials: C
authors.lastname: Zihni
authors.affiliation: Randall Division of Cell & Molecular Biophysics, New Hunt's House, Guy's Campus, Kings College London, London SE11UL, UK. Electronic address: stephen.terry@kcl.ac.uk.
authors.forename: Stephen James
authors.initials: SJ
authors.lastname: Terry
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016764:Cell Polarity; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction; D019108:Tight Junctions / Q000201:enzymology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D020741:rho GTP-Binding Proteins
keywords: Cancer; GAP; GEF; RhoGTPase; Signalling