The diacylglycerol kinase ?/atypical PKC/?1 integrin pathway in SDF-1? mammary carcinoma invasiveness.

ABSTRACT: Diacylglycerol kinase ? (DGK?), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGK? activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of ?5?1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGK? mediates SDF-1?-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1? stimulation, DGK? is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1? induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGK? promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGK? by promoting Rac-mediated protrusion elongation and localized recruitment of ?1 integrin and MMP-9. We finally demonstrate that activation of DGK?, atypical PKCs signaling and ?1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1? induced DGK? - atypical PKC - ?1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells.

SUBMITTER: Rainero E 

PROVIDER: S-EPMC4041662 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature