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Integrins uncouple Src-induced morphological and oncogenic transformation

Stephan Huveneers1, Serdar Arslan, Bob van de Water

  • 1Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands.

The Journal of Biological Chemistry
|March 11, 2008
PubMed

Insights

Activated c-Src in epithelial cells causes cancer and cell shape changes. Integrins regulate these processes through distinct pathways, separating oncogenic from morphological transformation.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Activated c-Src mutants in epithelial cells induce tumorigenicity and significant morphological changes.
  • Previous work showed integrin alphaVbeta3 supports Src-mediated oncogenic transformation via its cytoplasmic tail.

Purpose of the Study:

  • To investigate the distinct roles of integrins in Src-mediated oncogenic versus morphological transformation.
  • To elucidate the specific mechanisms by which beta1 and beta3 integrins influence Src-induced cellular alterations.

Main Methods:

  • Utilized activated c-Src mutants in epithelial cells.
  • Employed chimeric integrin subunits to map functional domains.
  • Analyzed cell morphology, cell-cell contacts, spreading, stress fibers, focal contacts, and podosome formation.
  • Investigated integrin phosphorylation and Rho-mediated contractility.

Main Results:

  • The interaction between Src and integrin alphaVbeta3's beta3 cytoplasmic tail is crucial for oncogenic transformation but not morphological changes.
  • Beta3 integrins, but not beta1, can prevent Src-induced cell rounding, requiring the beta3 extracellular domain.
  • Podosome assembly is independent of beta3 phosphorylation but requires beta1 phosphorylation to inhibit Rho-mediated contractility.

Conclusions:

  • Integrins regulate Src-mediated oncogenic and morphological transformations through separable molecular pathways.
  • Beta1 and beta3 integrins play distinct, context-dependent roles in modulating Src-induced cellular plasticity and tumor formation.

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