1. alpha v integrin processing interferes with the cross-talk between alpha v beta 5/beta 6 and alpha 2 beta 1 integrins
- Author
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Defilles, Céline, Montero, Marie-Pierre, Lissitzky, Jean-Claude, Rome, Sophie, Siret, Carole, Luis, José, Andre, Frédéric, Rigot, Veronique, Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Mécanisme Moléculaire du Diabète (MMD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), and This work was supported by Inserm, the University of Aix-Marseille and the 'Canceropole Provence Alpes Cote d'Azur'.
- Subjects
endoproteolytic cleavage ,integrin activation ,cell migration ,[SDV]Life Sciences [q-bio] ,cross-talk ,convertase ,phosphoinositide 3-kinase (PI3K) - Abstract
International audience; 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 alpha v beta 5/beta 6 integrin represses alpha 2 beta 1-dependent cell migration. The alpha v subunits undergo an endoproteolytic cleavage by protein convertases, whose role in tumoral invasion has remained controversial. Results. Inhibition of convertases by the convertase inhibitor alpha 1-PDX (alpha 1-antitrypsin Portland variant), leading to the cell-surface expression of an uncleaved form of the av integrin, stimulated cell migration toward type I collagen. Under convertase inhibition, alpha 2 beta 1 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 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 beta 1 integrins and to their location in larger focal-adhesion structures. The endoproteolytic cleavage of av subunits is necessary for alpha v beta 5/beta 6 integrin to control alpha 2 beta 1 function and could thus play an essential role in colon cancer cell migration.
- Published
- 2011