Format

Send to

Choose Destination
Oncotarget. 2015 Feb 10;6(4):1920-41.

Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways.

Author information

1
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
2
Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
3
Mass Spectrometry Research Facility CRL, Department of Chemistry, University of Oxford, Oxford, UK.
4
Centre for Omic Sciences, Rovira i Virgili University, Reus, Spain.
5
Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, Madrid, Spain.
6
The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, Oxford, UK.
7
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.

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 HIF1α and HIF2α. HIF1α 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 HIF1α 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 HIF1α in these processes, we used HCT116 colorectal cancer cells expressing endogenous HIF1α and cells in which the hif1α gene was deleted to characterize HIF1α-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 HIF1α-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 HIF1α.

PMID:
25605240
PMCID:
PMC4385826
DOI:
10.18632/oncotarget.3058
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center