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

Alessandro Valli, Miguel Rodriguez, Loukas Moutsianas, Roman Fischer, Vita Fedele, Hong Lei Huang, Ruud Van Stiphout, Dylan Jones, Michael Mccarthy, Maria Vinaxia, Kaori Igarashi, Maya Sato, Tomoyoshi Soga, Francesca Buffa, James Mccullagh, Oscar Yanes, Adrian Harris, Benedikt Kessler

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1920-1941
Number of pages22
JournalOncotarget
Volume6
Issue number4
Publication statusPublished - 2015

Fingerprint

Phenotype
Lipids
Neoplasms
Stearates
Pentose Phosphate Pathway
Metabolomics
Citric Acid Cycle
Palmitates
Glycolysis
Metabolic Networks and Pathways
Glycogen
Lipid Metabolism
Biochemistry
Proteomics
Oxidation-Reduction
Hypoxia
Colorectal Neoplasms
Fatty Acids
Membranes
Genes

Keywords

  • Cancer metabolism
  • Fatty acids
  • HIF1α
  • HIF2α
  • Hypoxia
  • Kennedy pathway
  • Lipidomics
  • PAF

ASJC Scopus subject areas

  • Oncology

Cite this

Valli, A., Rodriguez, M., Moutsianas, L., Fischer, R., Fedele, V., Huang, H. L., ... Kessler, B. (2015). Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways. Oncotarget, 6(4), 1920-1941.

Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways. / Valli, Alessandro; Rodriguez, Miguel; Moutsianas, Loukas; Fischer, Roman; Fedele, Vita; Huang, Hong Lei; Van Stiphout, Ruud; Jones, Dylan; Mccarthy, Michael; Vinaxia, Maria; Igarashi, Kaori; Sato, Maya; Soga, Tomoyoshi; Buffa, Francesca; Mccullagh, James; Yanes, Oscar; Harris, Adrian; Kessler, Benedikt.

In: Oncotarget, Vol. 6, No. 4, 2015, p. 1920-1941.

Research output: Contribution to journalArticle

Valli, A, Rodriguez, M, Moutsianas, L, Fischer, R, Fedele, V, Huang, HL, Van Stiphout, R, Jones, D, Mccarthy, M, Vinaxia, M, Igarashi, K, Sato, M, Soga, T, Buffa, F, Mccullagh, J, Yanes, O, Harris, A & Kessler, B 2015, 'Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways', Oncotarget, vol. 6, no. 4, pp. 1920-1941.
Valli A, Rodriguez M, Moutsianas L, Fischer R, Fedele V, Huang HL et al. Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways. Oncotarget. 2015;6(4):1920-1941.
Valli, Alessandro ; Rodriguez, Miguel ; Moutsianas, Loukas ; Fischer, Roman ; Fedele, Vita ; Huang, Hong Lei ; Van Stiphout, Ruud ; Jones, Dylan ; Mccarthy, Michael ; Vinaxia, Maria ; Igarashi, Kaori ; Sato, Maya ; Soga, Tomoyoshi ; Buffa, Francesca ; Mccullagh, James ; Yanes, Oscar ; Harris, Adrian ; Kessler, Benedikt. / Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways. In: Oncotarget. 2015 ; Vol. 6, No. 4. pp. 1920-1941.
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