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Insulin‐like growth factor‐I receptor, E‐cadherin and αv integrin form a dynamic complex under the control of α‐catenin
Author(s) -
Caici Alexandra,
Steelant Wim,
Rigot Véronique,
KhomitchBaud Alexandra,
BoutaghouCherid Hikma,
Bruyneel Erik,
Van Roy Frans,
Garrouste Françoise,
Pommier Gilbert,
André Frédéric
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23164
Subject(s) - integrin , cadherin , microbiology and biotechnology , cell migration , cell adhesion molecule , extracellular matrix , catenin , biology , cell adhesion , cancer research , growth factor , cell , receptor , chemistry , signal transduction , wnt signaling pathway , biochemistry
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 αv 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 α‐catenin, were used as models. Interactions between E‐cadherin, αv 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 αv integrin, E‐cadherin and IGF‐IR form a ternary complex in both cultured cancer cells and human normal colonic mucosa. α‐Catenin regulates the scaffolding of this complex. IGF‐IR ligation by IGF‐I induces the disruption of the complex and the relocalization of αv 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 αv 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. © 2007 Wiley‐Liss, Inc.