Integrins and E-cadherin cooperate with IGF-I to induce migration of epithelial colonic cells.
Although the detailed mechanisms of cell migration remain largely unknown, it is now clear that growth factors and cell adhesion molecules are crucial for this process. We have shown that type I insulin-like growth factor (IGF-I) promotes migration of human colonic tumour cells. Since morphological analysis suggested an involvement of adhesion molecules, we have now examined the role of integrins (cell-matrix adhesion molecules) and E-cadherin/catenins complex (cell-cell adhesion molecules) in the IGF-I-induced migration. Using a monolayer wounding assay, we have determined that, except for alpha2beta1, all of the integrins expressed in HT29-D4 cells are involved in the induced cell migration. Immunofluorescence studies revealed that upon IGF-I stimulation the integrins reorganized at the leading edge of migrating cells. We also demonstrate that E-cadherin is involved in cell migration. A rapid tyrosine phosphorylation of E-cadherin and beta-catenin was detected upon IGF-I stimulation. Tyrosine phosphorylation was associated with reduced membranous expression of E-cadherin and promotion of cell motility, suggesting a regulation of the E-cadherin/catenins complex. This effect can be reversed by incubating cells with tyrosine kinase inhibitors. Taken together, our results suggest that IGF-I promotes colonic cell migration through reorganization of integrin receptors and through modulation of E-cadherin/catenins complex function.
André
F
F
UPRESA-CNRS 6032, Faculté de Pharmacie, Marseille, France.
Rigot
V
V
Thimonier
J
J
Montixi
C
C
Parat
F
F
Pommier
G
G
Marvaldi
J
J
Luis
J
J
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D019073:HT29 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018715:Microscopy, Video; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin
D000911:Antibodies, Monoclonal; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D016023:Integrins; D010446:Peptide Fragments; D015534:Trans-Activators; D051176:beta Catenin; C058957:insulin-like growth factor 1, des-(1-3)-; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I