Differential expression of GABARAPs in GBM renders temozolomide sensitivity in a p53-dependent manner

Glioblastoma (GBM) is one of the most debilitating and extremely aggressive tumors, with a median survival of less than a year. GBMs have high metastatic potential and frequently acquire chemoresistance. The current multimodal treatment approaches for GBM include surgical tumor resurrection, radiotherapy, and chemotherapy but these approaches leave the patient with long-term disabilities such as depletion of cognitive abilities, leukoencephalopathy, and recurrence in 6-8 months. Glioma cells are highly dependent on autophagy to survive and proliferate. Autophagy inhibition has proven to be a beneficial strategy for restricting glioma growth. However, the autophagy pathway cannot be efficiently targeted due to the lack of specific autophagy inhibitors. Understanding the vulnerabilities in autophagy gene expression can help to design better autophagy inhibitors. This study demonstrates the differential expression of GABARAP family members in low-grade glioma and GBM. Our study highlights the differential expression of GABARAP family members in response to autophagy inhibition and induction. Moreover, the knockdown of specific GABARAP family members enhanced proliferation and reduced temozolomide (TMZ) sensitivity of glial cells by decreasing the p53 expression. The selective expression pattern of GABARAP genes in Glioblastoma can be utilized to screen for patients who might respond better to temozolomide treatment. The differential expression of GABARAP family members highlights the subtle regulation of the autophagy pathway in response to environmental cues.