EMMPRIN regulates 1 integrin-mediated adhesion through Kindlin-3 in human melanoma cells

EMMPRIN is known to promote tumor invasion through extracellular matrix (ECM) degradation. Here we report that EMMPRIN can regulate melanoma cell adhesion to the ECM through an interaction with 1 integrin involving kindlin-3. In this study, EMMPRIN knockdown in the human melanoma cell line M10 using siRNA decreased cell invasion and significantly increased cell adhesion and spreading. A morphological change from a round to a spread shape was observed associated with enhanced phalloidin-labelled actin staining. In situ proximity ligation assay and co-immunoprecipitation revealed that EMMPRIN silencing increased the interaction of 1 integrin with kindlin-3, a focal adhesion protein. This was associated with an increase in 1 integrin activation and a decrease in the phosphorylation of the downstream integrin kinase FAK. Moreover, the expression at both the transcript and protein level of kindlin-3 and of 1 integrin was inversely regulated by EMMPRIN. EMMPRIN did not regulate either talin expression or its interaction with 1 integrin. These results are consistent with our in vivo demonstration that EMMPRIN inhibition increased 1 integrin activation and its interaction with kindlin-3. To conclude, these findings reveal a new role of EMMPRIN in tumor cell migration through ss 1 integrin/kindlin-3-mediated adhesion pathway.