title: An acidic extracellular pH induces Src kinase-dependent loss of beta-catenin from the adherens junction.
abstract: Little attention has been paid to the role of adherens junctions (AJs) in acidic extracellular pH (pHe)-induced cell invasion. Incubation of HepG2 cells in acidic medium (pH 6.6) induced cell dispersion from tight cell clusters, and this change was accompanied by downregulation of beta-catenin at cell junctions and a rapid activation of c-Src. Pretreatment with PP2 prevented the acidic pH-induced downregulation of beta-catenin at AJ and in the membrane fractions. The acidic pHe-induced c-Src activation increased tyrosine phosphorylation of beta-catenin and decreased the amount of beta-catenin-associated E-cadherin. The depletion of membrane-bound beta-catenin coincided with enhanced cell migration and invasion, and this acidic pHe-increased cell migration and invasion was prevented by PP2. In conclusion, this study characterizes a novel signaling pathway responsible for acidic microenvironment-promoted migration and invasive behaviors of cancer cells.
authors.affiliation: Far Eastern Memorial Hospital, Department of Surgery and Division of General Surgery, Taipei 220, Taiwan.
authors.forename: Kuo-Hsin
authors.initials: KH
authors.lastname: Chen
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Tung
authors.forename: Jiahn-Chun
authors.initials: JC
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chen
authors.forename: Shih-Horng
authors.initials: SH
authors.lastname: Huang
authors.forename: Seu-Mei
authors.initials: SM
authors.lastname: Wang
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism* / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010766:Phosphorylation; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*; D019061:src-Family Kinases / Q000494:pharmacology*
chemical_list: D015820:Cadherins; D051176:beta Catenin; D019061:src-Family Kinases