Abstract
The mechanisms by which growth factors cooperate with cell adhesion molecules to modulate epithelial cell motility remain poorly understood. Here, we investigated the role of the E-cadherin/catenin complex in insulin-like growth factor (IGF-I)-dependent cell migration and invasion. We used variants of the HCT-8 colon cancer family that differ in their expression of αE-catenin, an intracellular molecule that links the E-cadherin/catenin complex to the actin cytoskeleton. Migration was determined using a monolayer wound model and cell invasion by the penetration of the cells into type-I collagen gels. We showed that α-catenin-deficient cells were not able to migrate in cohort upon IGF-I stimulation. Transfection of these cells with α-catenin isoforms (αN- or αT-catenin) restored migratory response IGF-I. These results suggest that α-catenins are involved in the signal issued from the E-cadherin/catenin complex to regulate IGF-I-stimulated migration. In contrast, IGF-I promoted invasion of both α-catenin-deficient and α-catenin-expressing cells, indicating that α-catenin did not participate in the regulation of IGF-I-induced invasion. Inhibition of E-cadherin function by treatment with MB-2 monoclonal antibodies inhibited both IGF-I-dependent cell migration and invasion. Taken together, our results indicate that functional α-catenin is essential for migration but not for invasion, while E-cadherin is involved in both phenomena.
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Acknowledgements
This work was supported by the Association de la Recherche contre le Cancer (France), the Société de Secours des Amis des Sciences (France), the Fortis-Bank/Verzekeringen and the Fund for Scientific Research (FWO-Vlaanderen), Brussels, Belgium.
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André, F., Janssens, B., Bruyneel, E. et al. Alpha-catenin is required for IGF-I-induced cellular migration but not invasion in human colonic cancer cells. Oncogene 23, 1177–1186 (2004). https://doi.org/10.1038/sj.onc.1207238
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DOI: https://doi.org/10.1038/sj.onc.1207238
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