Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness

Abstract Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet be clarified. We report this study that secretory ECM1a induces through GPR motif binding integrin ?X?2 and activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP cassette subfamily G member 1 (ABCG1) transduces ECM1a-integrin interactive signaling facilitate phosphorylation AKT/FAK/Rho/cytoskeletal molecules confer cancer cell cisplatin resistance up-regulation CD326-mediated stemness. On contrary, non-secretory ECM1b binds myosin blocks its phosphorylation, impairing cytoskeleton-mediated tumorigenesis. Moreover, expression heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein favor alternative mRNA splicing generating ECM1a. ECM1a, ?X?2, ABCG1 hnRNPLL higher associates with poor survival, while good survival. These results highlight as potential targets for treating cancers ECM1-activated