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αv integrin processing interferes with the cross-talk between αvβ5/β6 and α2β1 integrins
Céline Defilles1, Marie-Pierre Montero, Jean-Claude Lissitzky
1Inserm, UMR 911, Centre de Recherche en Oncologie et Oncopharmacologie, F-13005 Marseille, France.
Biology of the Cell
|July 27, 2011
Summary
Inhibiting convertase activity promotes colon cancer cell migration by up-regulating beta-1 integrins. This process involves enhanced signaling pathways and focal adhesion structures, independent of PI3K/Akt.
Area of Science:
- Cell biology
- Molecular biology
- Cancer research
Background:
- Integrin cross-talk regulates cell functions.
- Alpha-v (αv) integrin subunits are cleaved by protein convertases.
- This cleavage impacts tumoral invasion, though its role is debated.
Purpose of the Study:
- Investigate the role of alpha-v (αv) integrin cleavage in cell migration.
- Determine the signaling pathways involved in convertase inhibition-induced migration.
Main Methods:
- Used a convertase inhibitor (α1-PDX) to block alpha-v (αv) integrin cleavage.
- Assessed cell migration towards type I collagen.
- Analyzed phosphorylation of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK).
Main Results:
- Inhibiting convertases stimulated cell migration and alpha-2-beta-1 (α2β1) integrin engagement.
- Enhanced phosphorylation of FAK and MAPK was observed.
- Increased activated beta-1 (β1) integrin levels were found in larger focal adhesions, independent of the PI3K/Akt pathway.
Conclusions:
- Convertase inhibition up-regulates beta-1 (β1) integrins and promotes their localization in larger focal adhesions, increasing cell migration.
- Alpha-v (αv) integrin cleavage is crucial for alpha-v-beta-5/beta-6 (αvβ5/β6) integrin to regulate alpha-2-beta-1 (α2β1) function.
- This pathway may play a significant role in colon cancer cell migration.
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