The roles of mTOR complex 2 in lipid metabolism of brain cancer cell lines

Abstract

Background: Glioblastoma (GBM) is the most aggressive brain cancer, classified as a high-grade glioma found in the central nervous system (CNS). Metabolic reprogramming influences GBM, especially lipid metabolism. Increased lipid synthesis provides energy for cancer cells. Furthermore, activation of different pathways in lipid metabolism supports cell proliferation. mTORC1/2, a protein kinase, plays a role in lipid metabolism. Previous studies show that mTORC1 is involved in lipid regulation, while the functions of mTORC2 remain less well-defined.

Objective: To investigate the roles of mTORC2 in regulating lipid metabolism in GBM.

Methods: The U-87MG cells were treated with 0.1 µM rapamycin and 2 µM AZD8055 as mTORC1 and mTORC1/ 2 inhibitors, respectively. The expression of phosphorylated proteins targeted downstream of mTORC2 was measured by western blot. Lipid droplets in cells were stained with oil red o, and the amount of lipids was investigated using lipid extraction. The relative gene expressions were identified using RT-qPCR, and cell proliferation in GBM was measured by MTS assay.

Results: The expression of protein p-AKT-Ser473, a downstream target of mTORC2, was decreased with AZD8055 treatment. The outcomes related to lipids showed a reduction in lipid droplets and lower lipid contents in U-87MG cells treated with AZD8055, along with a decrease in gene expressions involved in lipid metabolism. These findings are consistent with significantly reduced cell proliferation, indicating that mTORC2 may regulate lipid processes in GBM, leading to brain tumor progression.

Conclusion: Both mTORC1 and mTORC2 are involved in lipid metabolism, leading to brain cancer progression.