TIGAR promotes growth, survival and metastasis through oxidation resistance and AKT activation in glioblastoma.

Abstract

Glioblastoma has a poor prognosis and is one of the most lethal types of cancer in the world. TP53 induced glycolysis regulatory phosphatase (TIGAR) is upregulated in various types of cancer. Therefore, the present study investigated the role of TIGAR in glioblastoma. TIGAR expression was measured in glioma samples and cell lines using immunohistochemistry and western blotting. Reduced nicotinamide adenine dinucleotide phosphate (NADPH), glutathione, malondialdehyde and intracellular reactive oxygen species levels were detected to measure oxidative stress in U-87MG cells following short hairpin RNA (shRNA)-mediated knockdown of TIGAR. Cell viability was determined using an MTT assay for TIGAR-overexpression vector- and TIGAR-shRNA-transfected U-87MG cells. Apoptosis was assessed to evaluate whether TIGAR knockdown sensitized cells to the antitumor effects of temozolomide (TMZ). Migration, invasion and epithelial-mesenchymal transition (EMT) were further assessed using Transwell and western blotting assays. A co-immunoprecipitation assay was used to detect the interaction between TIGAR and protein kinase B (AKT). The results of the present study revealed that TIGAR was positively associated with poor survival and was upregulated in glioblastoma. TIGAR knockdown significantly increased oxidative stress, decreased cell proliferation and exacerbated TMZ-induced apoptosis in U-87MG cells. Additionally, TIGAR knockdown decreased migration, invasion and EMT, and treatment of TIGAR-shRNA-transfected cells with NADPH had no effect on metastasis. In addition, TIGAR promoted AKT activation and bound to AKT. In conclusion, the present study demonstrated that TIGAR may promote glioblastoma growth and progression through oxidation resistance and AKT activation.