Tumor-Derived Mutated E-Cadherin Influences β-Catenin Localization and Increases Susceptibility to Actin Cytoskeletal Changes Induced by Pervanadate

E-cadherin participates in homophilic cell-to-cell adhesion and is localized to intercellular junctions of the adherens type. In the present study, we investigated the localization of adherens junction components in cells expressing mutant E-cadherin derivatives which had been previously cloned from diffuse-type gastric carcinoma. The mutations are in frame deletions of exons 8 or 9 and a point mutation in exon 8 and affect the extracellular domain of E-cadherin. Our findings indicate that E-cadherin mutated in exon 8 causes β-catenin staining at lateral cell-to-cell contact sites and, in addition, abnormally located β-catenin in the perinuclear region. Moreover, the various mutant E-cadherin derivatives increased the steady-state levels of α- and β-catenin and were found in association with these catenins even after induction of tyrosine phosphorylation by pervanadate. Sustained pervanadate treatment led, however, to rounding-up of cells and induction of filopodia, changes which were first detectable in ...