EMMPRIN regulates β 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 β 1 integrin involving kindlin‐3. In this study, EMMPRIN knockdown in the human melanoma cell line M10 using si RNA 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 β 1 integrin with kindlin‐3, a focal adhesion protein. This was associated with an increase in β 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 β 1 integrin was inversely regulated by EMMPRIN . EMMPRIN did not regulate either talin expression or its interaction with β 1 integrin. These results are consistent with our in vivo demonstration that EMMPRIN inhibition increased β 1 integrin activation and its interaction with kindlin‐3. To conclude, these findings reveal a new role of EMMPRIN in tumor cell migration through ß1 integrin/kindlin‐3‐mediated adhesion pathway.