Abstract
Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to 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 that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was 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 play important 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 migration capacity of human brain glioma cells.
Highlights
Malignant gliomas, one of the most common tumors in human brain, are highly infiltrative and invasive tumors (Wen and Kesari, 2008)
We investigated the effects of mda9/syntenin on human brain glioma cells migration
Mda-9/syntenin could upregulate the phosphorylation of focal adhesion kinase (FAK) at tyrosine 397, 576, 925 sites
Summary
One of the most common tumors in human brain, are highly infiltrative and invasive tumors (Wen and Kesari, 2008). Many studies showed that many factors were involved in the invasion of glioma, including adhesion molecules, extracellular matrix (ECM), protease system and angiogenesis, the exact molecular mechanism and process of the invasive growth of glioma has not been clearly elucidated (Salhia et al, 2006; Wang et al, 2011). Mda-9/ syntenin has been considered to be a positive regulator of tumor cell progression in human melanoma and other tumors (Rondepierre et al, 2010). Mda-9/syntenin regulates cell migration and invasion through focal adhesion kinase (FAK)-dependent signaling pathways, including c-Jun N-terminal kinase (JNK) and NFkappaB (NF-κB) (Boukerche et al, 2005; Boukerche et al, 2007; Hwangbo et al.). Mda-9/syntenin may interacts with c-Src and lead to an increase in FAK/c-Src complex formation and c-Src activation and enhanced
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