alpha v integrin processing interferes with the cross-talk between alpha v beta 5/beta 6 and alpha 2 beta 1 integrins

作者:Defilles Celine; Montero Marie Pierre; Lissitzky Jean Claude; Rome Sophie; Siret Carole; Luis Jose; Andre Frederic; Rigot Veronique*
来源:Biology of the Cell, 2011, 103(11): 519-529.
DOI:10.1042/BC20100147

摘要

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.

  • 出版日期2011-11

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