Abstract 5343: The HIV shell protein Gp120 stimulates U87 glioma cell proliferation through the activation of glycolysis

Patients infected with human immunodeficiency virus (HIV) are more prone to develop cancers, including glioblastomas (GBM). The median survival of GBM patients with HIV is significantly shorter compared to HIV-negative GBM patients, despite the fact that they receive the same treatments. This indicates that HIV infection is associated with more aggressive tumor behavior and with treatment resistance. Taking into account that HIV itself is not found in GBM specimens, the nature of the GBM-HIV association remains poorly understood and the underlying molecular mechanism is still unknown. Here we study the effect of Gp120, a glycoprotein found in the HIV shell, on GBM cell growth and chemotherapeutic resistance. U87 glioma cells were used in this study. Flow cytometry analyses based on 7-aminoactinomycin D staining and viability assays were used for identification of cell cycle, proliferation rates, and resistance to temozolomide (TMZ). Combined proteomics, metabolomics, and western blot approaches together with colorimetric pyruvate kinase activity assays were used for evaluation of metabolic pathways. U87 cells treated with Gp120 (200ng/ml) for 10 days showed higher proliferation rates and increased cell survival in response to treatment with TMZ (100µM) compared to un-treated cells. Quantitative proteomics studies using isobaric tags and western blot analysis identified expression up-regulation of several glycolytic enzymes, including enolase 2, pyruvate kinase, hexokinase, and glyceraldehyde 3-phosphate dehydrogenase in Gp120 treated U87 cells. Additionally, metabolite analysis revealed an increase of pyruvate, amino acid and lipid synthesis, together with reduction of protein degradation, in response to treatment with Gp120. In summary, we demonstrated that Gp120 promoted proliferation and resistance to TMZ in U87 cells through the activation of glycolysis, resulting in increased protein and lipid synthesis This research was made possible by NIH grant numbers: 1SC2GM102040, R25GM110513, INBRE-PR NIH Grant 8P20GM103475, the UCC RCMI Biomedical Proteomics Facility grant G12MD007583 and US Department of Education Grant number P031S130068. Citation Format: Gabriel Valentin-Guillama, Sheila Lopez, Jose Perez, Luis Cubano, Natalia Chorna, Jeffrey Harrison, Nawal Boukli, Lilia Kucheryavykh. The HIV shell protein Gp120 stimulates U87 glioma cell proliferation through the activation of glycolysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5343. doi:10.1158/1538-7445.AM2017-5343