The activation of CD99 inhibits cell-extracellular matrix adhesion by suppressing β1 integrin affinity

Abstract

CD99 is known to be involved in the regulation of cell-celladhesion. However, it remains unclear whether CD99 controlscell-extracellular matrix adhesion. In this study, the effects ofCD99 activation on cell-extracellular matrix adhesion wereinvestigated. It was found that engagement of CD99 with thestimulating antibody YG32 downregulated the adhesion ofMCF-7 cells to fibronectin, laminin and collagen IV in adose-dependent manner. The CD99 effect on cell-ECM adhesionwas inhibited by overexpression of the dominant negativeform of CD99 or CD99 siRNA transfection. Treatment of cellswith Mn2+ or by β1 integrin-stimulating antibody restored theinhibitory effect of CD99 on cell-ECM adhesion. Cross-linkingCD99 inactivated β1 integrin through conformational change.CD99 activation caused dephosphorylation at Tyr-397 in FAK,which was restored by the β1 stimulating antibody. Taken together,these results provide the first evidence that CD99 inhibitscell-extracellular matrix adhesion by suppressing β1 integrinaffinity. [BMB reports 2012; 45(3): 159-164]

Keywords

• β1 integrin
• CD99
• Cell-ECM adhesion
• Conformational change
• FAK