Tumor-derived mutated E-cadherin influences β-catenin localization and increases susceptibility to actin cytoskeletal changes induced by pervanadate

Birgit Luber, Sonja Candidus, Gabriele Handschuh, Edith Mentele, Peter Hutzler, Stephan Feller, Jan Voss, Heinz Höfler, Karl Friedrich Becker

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

E-cadherin participates in hemophilic 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 cells expressing E-cadherin mutated in exon 8. The deterioration of the cell contact was not accompanied with disassembly of the E-cadherin-catenin complex. Based on these observations, we propose a model whereby in the presence of mutant E-cadherin tyrosine phosphorylation of components of the cell adhesion complex triggers loss of cell-to-cell contact and actin cytoskeletal changes which are not caused by the disruption of the E-cadherin-catenin complex per se, but instead might be due to phosphorylation of other signaling molecules or activation of proteins involved in the regulation of the actin cytoskeleton.

Original languageEnglish
Pages (from-to)391-408
Number of pages18
JournalCell Adhesion and Communication
Volume7
Issue number5
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Catenin
  • Cell adhesion
  • E-cadherin
  • Gastric carcinoma
  • Tyrosine phosphorylation

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