Characterization of aberrant mTOR signaling pathway in U87MG glioblastoma cell line by quantitative phosphoproteomics

This study focused on the aberrant mTORC2 signaling pathway in glioblastoma cells, specifically using U87MG grade IV glioma cells. Researchers used quantitative phosphoproteomics to analyze the effects of mTORC1/2 inhibitor AZD8055 and mTORC1 inhibitor rapamycin, identifying numerous phosphoproteins as mTORC2 downstream targets. The study revealed that mTORC2 inhibition is involved in double-strand break (DSB) repair, particularly through the phosphorylation of BABAM1 (MERIT40) at Ser29, which is crucial for DNA damage response and cancer cell survival. Inactivation of mTORC2 reduced DNA repair activities and promoted apoptosis in cancer cells. Additionally, γH2AX phosphorylation at Ser139 was identified as a potential downstream target of mTORC2, associated with BABAM1 in DSB repair. These findings enhanced the understanding of mTORC2's role in oncogenic DNA damage response and suggested potential for developing specific mTORC2-targeted treatments for brain cancer.