Lumican inhibits cell migration through alpha2beta1 integrin.
Fiche publication
Date publication
octobre 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BREZILLON Stéphane
Tous les auteurs :
Zeltz C, Brezillon S, Kapyla J, Eble JA, Bobichon H, Terryn C, Perreau C, Franz CM, Heino J, Maquart FX, Wegrowski Y
Lien Pubmed
Résumé
Lumican, an extracellular matrix protein of the small leucine-rich proteoglycan family, has been shown to impede melanoma progression by inhibiting cell migration. In the present study, we show that lumican targets alpha2beta1 integrin thereby inhibiting cell migration. A375 melanoma cells were transfected with siRNA directed against the alpha2 integrin subunit. Compared to A375 control cells, the anti-migratory effect of lumican was abrogated on transfected A375 cells. Moreover, lumican inhibited the chemotactic migration of Chinese hamster ovary (CHO) cells stably transfected with alpha2 integrin subunit (CHO-A2) but not that of wild-type CHO cells (CHO-WT) lacking this subunit. In contrast to CHO-WT cells, we observed in time-lapse microscopy a decrease of CHO-A2 cell migration speed in presence of lumican. Focal adhesion kinase phosphorylated at tyrosine-397 (pFAK) and total FAK were analysed in CHO-WT and CHO-A2 cells. A significant decrease of the ratio pFAK/FAK was shown in presence of recombinant human lumican. Using solid phase assays, a direct binding between lumican and the alpha2beta1 integrin was demonstrated. This interaction did not involve the glycan moiety of lumican and was cation independent. Lumican was also able to bind the activated I domain of the alpha2 integrin subunit with a K(d)>/=200nM. In conclusion, we demonstrated for the first time that the inhibition of cell migration by lumican depends on a direct binding between the core protein of lumican and the alpha2beta1 integrin.
Référence
Exp Cell Res. 2010 Oct 15;316(17):2922-31