1. αv integrin processing interferes with the cross-talk between αvβ5/β6 and α2β1 integrins.
- Author
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Defilles C, Montero MP, Lissitzky JC, Rome S, Siret C, Luis J, André F, and Rigot V
- Subjects
- Cell Adhesion, Cell Movement, Collagen Type I metabolism, Focal Adhesion Protein-Tyrosine Kinases metabolism, Humans, Mitogen-Activated Protein Kinases metabolism, Phosphatidylinositol 3-Kinase metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, alpha 1-Antitrypsin biosynthesis, Antigens, Neoplasm metabolism, Integrin alpha2beta1 metabolism, Integrin alphaV metabolism, Integrins metabolism, Receptors, Vitronectin metabolism
- Abstract
Background Information: Previous studies have reported that cross-talk between integrins may be an important regulator of integrin-ligand binding and subsequent signalling events that control a variety of cell functions in many tissues. We previously demonstrated that αvβ5/β6 integrin represses α2β1-dependent cell migration. The αv subunits undergo an endoproteolytic cleavage by protein convertases, whose role in tumoral invasion has remained controversial., Results: Inhibition of convertases by the convertase inhibitor α1-PDX (α1-antitrypsin Portland variant), leading to the cell-surface expression of an uncleaved form of the αv integrin, stimulated cell migration toward type I collagen. Under convertase inhibition, α2β1 engagement led to enhanced phosphorylation of both FAK (focal adhesion kinase) and MAPK (mitogen-activated protein kinase). This outside-in signalling stimulation was associated with increased levels of activated β1 integrin located in larger than usual focal-adhesion structures and a cell migration that was independent of the PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) pathway., Conclusions: The increase in cell migration observed upon convertases inhibition appears to be due to the up-regulation of β1 integrins and to their location in larger focal-adhesion structures. The endoproteolytic cleavage of αv subunits is necessary for αvβ5/β6 integrin to control α2β1 function and could thus play an essential role in colon cancer cell migration.
- Published
- 2011
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