The Src-induced mesenchymal state in late-stage colon cancer cells

Egle Mcdonald, Egle Avizienyte, Valerie G. Brunton, Valerie J. Fincham, Margaret C. Frame

    Research output: Contribution to journalArticlepeer-review


    One major function of elevated Src kinase in epithelial cancer cells is to drive adhesion changes that are associated with the mesenchymal transition and metastasis [Jones et al., Br J Cancer 2002;87:1128-1135]. Here we review recent work that describes Src-induced shape changes, and the mechanisms involved, in cells derived from a model of colon cancer metastasis. Src activity in these cells is associated with formation and dynamic regulation of integrin adhesions and disorganization of E-cadherin-dependent cell-cell contacts. Furthermore, Src-induced deregulation of E-cadherin requires integrin signalling [Avizienyte et al., Nat Cell Biol 2002;4:632-638], demonstrating a complex interdependence between integrin- and cadherin-associated adhesion changes induced by Src. The integrin-induced signals that co-operate with Src to cause deregulation of cadherin-dependent cell-cell contacts include activation of the MEK/ERK and MLCK/myosin activities. Inhibition of this pathway suppresses integrin complexes formed on fibronectin, while promoting E-cadherin redistribution to sites of cell-cell contacts [Avizienyte et al., Mol Biol Cell 2004;15:2794-2803]. Also, in embryonic fibroblasts that express N-cadherin (which is normally diffusely cytoplasmic as these cells maintain a fibroblastic morphology) suppressing integrin signalling and inhibiting the MEK/ERK/MLCK/myosin pathway relocalizes N-cadherin to cell-cell contacts. Our recent data therefore imply an important, and perhaps general, role for spatially controlled contractility in suppressing normal cadherin localization and inducing a mesenchymal-like phenotype. Copyright © 2005 S. Karger AG.
    Original languageEnglish
    Pages (from-to)73-80
    Number of pages7
    JournalCells Tissues Organs
    Issue number1-2
    Publication statusPublished - 2005


    • Adhesion
    • Cadherin
    • Epithelial-mesenchymal transition
    • Integrins
    • Src


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