CD44-Src signaling promotes invadopodia formation in prostate cancer (PC3) cells

Abstract

IntroductionSrc kinase activation has been rep orted in unrelated human cancers and considered a possible target of anti-invasive therapies. Our aim here is to identify the relationship of Src kinase with CD44-signalling. Although CD44 is implicated in the invasion of cancer cells, its role in invadopodia formation needs further elucidation. Materials and MethodsTo study the role of Src, PC3 cells were transfected with Src constructs by adenoviral-mediated delivery. Gelatin degradation assay was performed to determine the invasive property of PC3 cells. Immunoblotting and immunostaining analyses were used to determine complex interaction of proteins with CD44. PC3 cells knockdown of CD44 were used to characterize the function of CD44 in invadopodia formation and invasion. ResultsIn this study, we show that expression of constitutively-active Src in prostate cancer 3 (PC3) cells significantly increased the invasiveness of PC3 cells via increasing the number of invadopodia as a result of CD44-associated complex (Src-Cortactin-Wiskott-Aldrich Syndrome Protein WASP) forma tion. The inhibition of invadopodial structures in CD44 knockdown PC3 cells resulted in reduced invasion. ConclusionBased on these results, we conclude that CD44-Src-cortactin-WASP is an invasion promoting complex. Proteins in this complex are relevant targets for intervening invadopodia formation and migration/invasion processes in prostate cancer cells.