title: Tumor-derived mutated E-cadherin influences beta-catenin localization and increases susceptibility to actin cytoskeletal changes induced by pervanadate.
abstract: 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 beta-catenin staining at lateral cell-to-cell contact sites and, in addition, abnormally located beta-catenin in the perinuclear region. Moreover, the various mutant E-cadherin derivatives increased the steady-state levels of alpha- and beta-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 phoshorylation 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.
authors.affiliation: GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Pathologie, Neuherberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Luber
authors.forename: S
authors.initials: S
authors.lastname: Candidus
authors.forename: G
authors.initials: G
authors.lastname: Handschuh
authors.forename: E
authors.initials: E
authors.lastname: Mentele
authors.forename: P
authors.initials: P
authors.lastname: Hutzler
authors.forename: S
authors.initials: S
authors.lastname: Feller
authors.forename: J
authors.initials: J
authors.lastname: Voss
authors.forename: H
authors.initials: H
authors.lastname: Höfler
authors.forename: K F
authors.initials: KF
authors.lastname: Becker
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D051180:Desmoplakins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000235:genetics; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin
chemical_list: D000199:Actins; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; C076715:pervanadate; D014638:Vanadates; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases; D000095002:Delta Catenin