MDA-9/Syntenin promotes glioma cell proliferation and invasion via exosome-mediated activation of the PI3K-AKT signaling pathway

Exosomes, lipid bilayer-enclosed extracellular vesicles, transfer bioactive molecules to mediate intercellular communication and tumour progression. Melanoma differentiation-associated gene 9 (MDA-9/Syntenin) regulates exosome biogenesis, but its role in glioma-derived exosomes remains poorly understood, with prior studies focusing primarily on MDA-9's intracellular functions in glioma cells. Here, we investigate MDA-9-mediated exosomal contributions to glioma pathogenesis. We found that MDA-9 is upregulated in glioma tissues, correlating with poor prognosis in glioma patients. Exosomes from MDA-9-overexpressing glioma cells significantly enhanced recipient glioma cell proliferation and invasion compared to controls. Mechanistically, these exosomes activated the PI3K-AKT pathway, upregulating MMP9 and c-MYC to drive cell proliferation and invasion. These findings reveal a novel role of the exosomal MDA-9-PI3K-AKT-MMP9/c-MYC axis in glioma progression, highlighting MDA-9 as a promising therapeutic target.