title: Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.
abstract: Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.
authors.affiliation: Department of Surgery II, Osaka University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shiozaki
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Y
authors.initials: Y
authors.lastname: Doki
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: H
authors.initials: H
authors.lastname: Oka
authors.forename: T
authors.initials: T
authors.lastname: Iwazawa
authors.forename: S
authors.initials: S
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Shimaya
authors.forename: M
authors.initials: M
authors.lastname: Takeichi
mesh_terms: D016227:Benzoquinones; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002460:Cell Line; D046508:Culture Techniques / Q000379:methods; D003598:Cytoskeletal Proteins / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000473:pathology*; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D005782:Gels; D006801:Humans; D047029:Lactams, Macrocyclic; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D010641:Phenotype; D010766:Phosphorylation; D019000:Phosphotyrosine; D011499:Protein Processing, Post-Translational; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D015534:Trans-Activators; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014410:Tumor Stem Cell Assay; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D014638:Vanadates / Q000494:pharmacology; D051178:alpha Catenin; D051176:beta Catenin
chemical_list: D016227:Benzoquinones; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D005782:Gels; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; D011809:Quinones; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D017828:Rifabutin; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; D004815:Epidermal Growth Factor; C020754:herbimycin; D066246:ErbB Receptors