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CD99 is known to be involved in the regulation of cell-cell adhesion. However, it remains unclear whether CD99 controls cell-extracellular matrix adhesion. In this study, the effects of CD99 activation on cell-extracellular matrix adhesion were investigated. It was found that engagement of CD99 with the stimulating antibody YG32 downregulated the adhesion of MCF-7 cells to fibronectin, laminin and collagen IV in a dose-dependent manner. The CD99 effect on cell-ECM adhesion was inhibited by overexpression of the dominant negative form of CD99 or CD99 siRNA transfection. Treatment of cells with Mn2+ or by β1 integrin-stimulating antibody restored the inhibitory effect of CD99 on cell-ECM adhesion. Cross-linking CD99 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 inhibits cell-extracellular matrix adhesion by suppressing β1 integrin affinity. [BMB reports 2012; 45(3): 159-164]

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