Switch from αvβ5 to αvβ6 integrin is required for CD9-regulated keratinocyte migration and MMP-9 activation

Our previous research found that tetraspanin CD9 is downregulated in migrating epidermis during wound healing, and CD9 downregulation contributes to keratinocyte migration via matrix metalloproteinase-9 (MMP-9) activation. However, little is known about the mechanisms involved in CD9-regulated keratinocyte migration and MMP-9 activation. In this study, we revealed that the expressions of integrin subunits beta 5 and beta 6 were regulated by CD9. Furthermore, CD9 silencing triggered the switch from alpha v beta 5 to alpha v beta 6 integrin in HaCaT keratinocytes and CD9 overexpression reversed the switch. Importantly, integrin alpha v beta 6 functional blocking antibody 10D5 significantly inhibited CD9 silencing-induced keratinocyte migration and MMP-9 activation, suggesting that the switch from alpha v beta 5 to alpha v beta 6 integrin plays a key role in CD9-regulated cell migration and MMP-9 activation in keratinocytes. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.