TRAM2 promotes the malignant progression of glioma through PI3K/AKT/mTOR pathway.

Molecular biomarkers play an important guidance role in the diagnosis and treatment of glioma. It has been found that TRAM2 (translocation associated membrane protein 2) drives human cancers development. Here we report that TRAM2 activity is required for malignancy properties of glioma. In this study, we demonstrated that TRAM2 is over-expressed in glioma and cell lines, particularly in the mesenchymal subtype, and glioma patients with high expression of TRAM2 is associated with poorer survival. Silencing of TRAM2 significantly suppresses glioma cell proliferation, invasion, migration and EMT in vitro, and inhibits tumorigenicity of glioma cell in vivo. We further identify that TRAM2 is positively associated with activation of the PI3K/AKT/mTOR signaling in glioma. 740Y-P, a PI3K activator, reversed the effects of TRAM2 silencing on glioma cell proliferation, invasion, migration and EMT process. Taken together, these findings establish that TRAM2/PI3K/AKT/mTOR signaling drives malignancy properties of glioma and indicate that TRAM2 may act as a potential therapeutic target for glioma.