title: αv integrin processing interferes with the cross-talk between αvβ5/β6 and α2β1 integrins.
abstract: BACKGROUND
  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.
authors.affiliation: Inserm, UMR 911, Centre de Recherche en Oncologie et Oncopharmacologie, F-13005 Marseille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Defilles
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Montero
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lissitzky
authors.forename: Sophie
authors.initials: S
authors.lastname: Rome
authors.forename: Carole
authors.initials: C
authors.lastname: Siret
authors.forename: José
authors.initials: J
authors.lastname: Luis
authors.forename: Frédéric
authors.initials: F
authors.lastname: André
authors.forename: Véronique
authors.initials: V
authors.lastname: Rigot
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D024042:Collagen Type I / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D039564:Integrin alphaV / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis
chemical_list: D000951:Antigens, Neoplasm; D024042:Collagen Type I; D038982:Integrin alpha2beta1; D039564:Integrin alphaV; D016023:Integrins; D019030:Receptors, Vitronectin; D000515:alpha 1-Antitrypsin; C113421:alpha 1-antitrypsin Portland; C064660:integrin alphaVbeta5; C073878:integrin alphavbeta6; D058539:Phosphatidylinositol 3-Kinase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases