Hypoxia induces a lipogenic cancer cell phenotype via HIF1?-dependent and -independent pathways.

ABSTRACT: The biochemistry of cancer cells diverges significantly from normal cells as a result of a comprehensive reprogramming of metabolic pathways. A major factor influencing cancer metabolism is hypoxia, which is mediated by HIF1? and HIF2?. HIF1? represents one of the principal regulators of metabolism and energetic balance in cancer cells through its regulation of glycolysis, glycogen synthesis, Krebs cycle and the pentose phosphate shunt. However, less is known about the role of HIF1? in modulating lipid metabolism. Lipids serve cancer cells to provide molecules acting as oncogenic signals, energetic reserve, precursors for new membrane synthesis and to balance redox biological reactions. To study the role of HIF1? in these processes, we used HCT116 colorectal cancer cells expressing endogenous HIF1? and cells in which the hif1? gene was deleted to characterize HIF1?-dependent and independent effects on hypoxia regulated lipid metabolites. Untargeted metabolomics integrated with proteomics revealed that hypoxia induced many changes in lipids metabolites. Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in a HIF1?-dependent fashion. Palmitate, stearate, PLD3 and PAFC16 were regulated in a HIF-independent manner. Our results demonstrate the impact of hypoxia on lipid metabolites, of which a distinct subset is regulated by HIF1?.

SUBMITTER: Valli A 

PROVIDER: S-EPMC4385826 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature