Mda-9/syntenin Promotes Human Brain Glioma Migration through Focal Adhesion Kinase (FAK)-JNK and FAK-AKT Signaling

Abstract

Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma andrestricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involvedin promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was usedto test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin.Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK)and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than thatof CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 sitewas not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated.Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively.and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways playimportant roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda-9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migrationcapacity of human brain glioma cells.