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alphavbeta5/beta6 integrin suppression leads to a stimulation of alpha2beta1 dependent cell migration resistant to

Céline Defilles1, Jean-Claude Lissitzky, Marie-Pierre Montero

  • 1INSERM UMR 911, Centre de Recherche en Oncologie Biologique et Oncopharmacologie, Aix-Marseille Université, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France.

Experimental Cell Research
|March 31, 2009
PubMed

Insights

Integrins alphavbeta5/beta6 normally limit alpha2beta1 function in cell migration. Removing alphav integrins enhances alpha2beta1-mediated migration and signaling, suggesting alphav integrins regulate alpha2beta1 activation.

Area of Science:

  • Cell biology
  • Molecular biology
  • Integrin signaling

Background:

  • Integrin crosstalk regulates cell functions, including migration.
  • Specific integrin pairs, alphavbeta5/beta6 and alpha2beta1, play roles in cell migration toward collagen.

Purpose of the Study:

  • To investigate the interplay between alphavbeta5/beta6 and alpha2beta1 integrins during cell migration.
  • To understand how alphavbeta5/beta6 integrins influence alpha2beta1 function and signaling.

Main Methods:

  • Used human colon cancer cell lines (HT29-D4, SW480).
  • Reduced alphav integrin expression via siRNA or lysosomal targeting.
  • Inhibited alphav integrin function using blocking antibodies or disintegrins.
  • Analyzed cell migration, focal adhesion, and signaling pathways (FAK, ERK1/2, PI3K/AKT).

Main Results:

  • Decreasing alphav integrin expression or function significantly enhanced alpha2beta1-dependent cell migration.
  • Enhanced migration was associated with focal adhesion rearrangements and increased FAK/ERK phosphorylation.
  • Activating alphavbeta5/beta6 integrins with TS2/16 antibody could overcome the alphavbeta5/beta6-dependent limitation of alpha2beta1.
  • Inhibition of PI3K or AKT had minimal impact on migration in the absence of alphav integrins.

Conclusions:

  • Integrins alphavbeta5/beta6 appear to repress alpha2beta1 integrin function, potentially by interfering with its activation process.
  • This repression influences cell signaling pathways regulating alpha2beta1-mediated migration.
  • Targeting alphav integrins could modulate alpha2beta1-driven cell migration and signaling.

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