Chen, Kuo-HsinKuo-HsinChenTung, Po-YuanPo-YuanTungWu, Jiahn-ChunJiahn-ChunWuChen, YingYingChen2011-02-112018-07-112011-02-112018-07-112008-08http://ntur.lib.ntu.edu.tw//handle/246246/223131Little 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 β-catenin at cell junctions and a rapid activation of c-Src. Pretreatment with PP2 prevented the acidic pH-induced downregulation of β-catenin at AJ and in the membrane fractions. The acidic pHe-induced c-Src activation increased tyrosine phosphorylation of β-catenin and decreased the amount of β-catenin-associated E-cadherin. The depletion of membrane-bound β-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. ? 2008 Elsevier Ireland Ltd. All rights reserved.en-USβ-Catenin; Acidic extracellular pH; Adherens junction; c-Src kinase; Cell migration; Invasion[SDGs]SDG34 amino 7 tert butyl 5 (4 chlorophenyl)pyrazolo[3,4 d]pyrimidine; beta catenin; protein tyrosine kinase; uvomorulin; article; cell culture; cell invasion; cell junction; cell migration; cell strain HepG2; controlled study; drug effect; gene activation; human; human cell; immunofluorescence; pH; priority journal; protein depletion; protein phosphorylation; Adherens Junctions; beta Catenin; Cadherins; Cell Line, Tumor; Cell Movement; Humans; Hydrogen-Ion Concentration; Phosphorylation; Signal Transduction; src-Family Kinasesjournal article10.1016/j.canlet.2008.03.005