Insulin-like growth factor-I receptor, E-cadherin and alpha v integrin form a dynamic complex under the control of alpha-catenin.
Dynamic crosstalk between cell adhesion molecules, extracellular matrix and soluble informative factors is essential for cancer cell migration and invasion. Here, we investigated the mechanisms by which the E-cadherin/catenin complex and alpha v integrin can modulate insulin-like growth factor-I (IGF-I)-induced cell migration. Human colon mucosa, human colon cancer cell lines, HT29-D4 and HCT-8 derivatives that differ in their expression of alpha-catenin, were used as models. Interactions between E-cadherin, alpha v integrin and IGF-I receptor (IGF-IR) were analyzed by coimmunoprecipitation and immunolocalization experiments. The impact of these interactions on cell mobility was determined by haptotaxis assays. We report that alpha v integrin, E-cadherin and IGF-IR form a ternary complex in both cultured cancer cells and human normal colonic mucosa. alpha-Catenin regulates the scaffolding of this complex. IGF-IR ligation by IGF-I induces the disruption of the complex and the relocalization of alpha v integrin from cell-cell contacts to focal contact sites. This perturbation is correlated with the observed increase in cell migration. These results suggest that regulation of the alpha v integrin/E-cadherin/IGF-IR scaffolding is essential for the modulation of cell mobility. Its alteration could be of major importance to sustain alterations in cell adhesion that occur during cancer cell invasion and metastasis.
Canonici
Alexandra
A
CISMET, FRE CNRS 2737, Universités d'Aix-Marseille I et II, Marseille, France.
Steelant
Wim
W
Rigot
Véronique
V
Khomitch-Baud
Alexandra
A
Boutaghou-Cherid
Hikma
H
Bruyneel
Erik
E
Van Roy
Frans
F
Garrouste
Françoise
F
Pommier
Gilbert
G
André
Frédéric
F
D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019073:HT29 Cells / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D055504:Insulin Receptor Substrate Proteins; D039564:Integrin alphaV / Q000378:metabolism*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D051178:alpha Catenin / Q000494:pharmacology*
D015820:Cadherins; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D039564:Integrin alphaV; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D051178:alpha Catenin; D017526:Receptor, IGF Type 1