Metabolic regulation of prolyl hydroxylase domain-containing protein and hypoxia-inducible factor in glioblastoma cells in-vitro

Abstract

Glioblastoma multiforme (GBM) is one of the most lethal tumors known to man. This lethality is partly attributable to its rapid growth, which creates intratumoral regions scarce of oxygen and nutrients. GBM adapts to oxygen scarcity by activating the hypoxic response via hypoxia-inducible factor (HIF), thereby ensuring their survival and progression. HIF, in turn, is tightly regulated by prolyl hydroxylase domain-containing proteins. This work aims to characterize metabolic factors that influence the function of prolyl hydroxylase domain-containing proteins in GBM, including the metabolites glutamine, glutamate and alpha-ketoglutarate, and the citric acid cycle enzyme isocitrate dehydrogenase.