An acidic extracellular pH induces Src kinase-dependent loss of beta-catenin from the adherens junction.
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.
Chen
Kuo-Hsin
KH
Far Eastern Memorial Hospital, Department of Surgery and Division of General Surgery, Taipei 220, Taiwan.
Tung
Po-Yuan
PY
Wu
Jiahn-Chun
JC
Chen
Ying
Y
Chen
Po-Chun
PC
Huang
Shih-Horng
SH
Wang
Seu-Mei
SM
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*
D015820:Cadherins; D051176:beta Catenin; D019061:src-Family Kinases