EMMPRIN regulates β1 integrin‐mediated adhesion through Kindlin‐3 in human melanoma cells. Issue 6 (16th April 2015)

• Record Type: Journal Article
• Authors: Delyon, Julie; Khayati, Farah; Djaafri, Ibtissem; Podgorniak, Marie‐Pierre; Sadoux, Aurélie; Setterblad, Niclas; Boutalbi, Zineb; Maouche, Kamel; Maskos, Uwe; Menashi, Suzanne; Lebbé, Céleste; Mourah, Samia
• Is Part Of: Experimental dermatology. Volume 24:Issue 6(2015:Jun.)
• Page Start: 443
• Page End: 448
• Publication Date: 2015-04-16
• Subjects: Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.12693
• Languages: English
• ISSNs: 0906-6705

Abstract

<abstract abstract-type="main" id="exd12693-abs-0001"> <title>Abstract</title> <p>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 <italic>β</italic>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. <italic>In situ</italic> proximity ligation assay and co‐immunoprecipitation revealed that EMMPRIN silencing increased the interaction of <italic>β</italic>1 integrin with kindlin‐3, a focal adhesion protein. This was associated with an increase in <italic>β</italic>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 <italic>β</italic>1 integrin was inversely regulated by EMMPRIN. EMMPRIN did not regulate either talin expression or its interaction with <italic>β</italic>1 integrin. These results are consistent with our <italic>in vivo</italic> demonstration that EMMPRIN inhibition increased <italic>β</italic>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.</p> </abstract>