Integrins and E‐cadherin cooperate with IGF‐I to induce migration of epithelial colonic cells

Abstract

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 (cellcell adhesion molecules) in the IGF-I-induced migration. Using a monolayer wounding assay, we have determined that, except for ␣2␤1, 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 ␤-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. Int.

Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines

“…In breast cancer cells, Guvakova and Surmacz (1997) have shown that IGFR1 enhances adherence via Ecadherin complexes. In colon cancer cells, both E- cadherin and integrins may cooperate with IGFR1 to enhance migration (Andre et al, 1999). Several lines of evidence suggest that direct interactions between integrin and IGFR1 signaling pathways exist.…”

Role of the IGF‐I receptor in the regulation of cell–cell adhesion: Implications in cancer development and progression

“…For instance, in C10 colorectal cancer cells, IGF-I-stimulated cell spreading, which was accompanied by tyrosine phosphorylation of beta-catenin, dissociation of beta-catenin from E-cad and translocation of beta-catenin from a sub-membrane to a cytoplasmic compartment (Playford et al, 2000). In addition, Andre' et al (1999) demonstrated enhanced tyrosine phosphorylation of beta-catenin upon IGF-I stimulation in an APC-mutated colorectal cancer cell line, HT29. This resulted in down-regulation of E-cad and increased cell motility.…”

Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways

“…For example, activation of IGF-IR and subsequent activation of PI3K and mitogen-activated protein kinase pathways induces motility of neuroblastoma cells (Meyer et al, 2001). By affecting integrin relocation and association of the E-cadherin/catenin complex with the cytoskeleton, IGF-I stimulates migration of epithelial colonic cells (Andre et al, 1999) and myeloma cells (Tai et al, 2003). IGF-IR controls lung carcinoma cell motility and invasion by coordinately regulating expression and activation of matrix metalloproteinase-2 (Zhang and Brodt, 2002).…”