The transcription factor HIF-1 plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis

Julian J. Lum, Thi Bui, Michaela Gruber, John D. Gordan, Ralph J. DeBerardinis, Kelly L. Covello, M. Celeste Simon, Craig B. Thompson

Research output: Contribution to journalArticle

231 Scopus citations

Abstract

Mammalian cells are believed to have a cell-intrinsic ability to increase glucose metabolism in response to hypoxia. Here we show that the ability of hematopoietic cells to up-regulate anaerobic glycolysis in response to hypoxia is dependent on receptor-mediated signal transduction. In the absence of growth factor signaling, hematopoietic cells fail to express hypoxia-inducible transcription factor (Hif-1α) mRNA. Growth factor-deprived hematopoietic cells do not engage in glucose-dependent anabolic synthesis and neither express Hif-1α mRNA nor require HIF-1α protein to regulate cell survival in response to hypoxia. However, HIF-1α is adaptive for the survival of growth factor-stimulated cells, as suppression of HIF-1α results in death when growing cells are exposed to hypoxia. Growth factor-dependent HIF-1α expression reprograms the intracellular fate of glucose, resulting in decreased glucose-dependent anabolic synthesis and increased lactate production, an effect that is enhanced when HIF-1α protein is stabilized by hypoxia. Together, these data suggest that HIF-1α contributes to the regulation of growth factor-stimulated glucose metabolism even in the absence of hypoxia.

Original languageEnglish (US)
Pages (from-to)1037-1049
Number of pages13
JournalGenes and Development
Volume21
Issue number9
DOIs
StatePublished - May 1 2007

Keywords

  • Cell survival
  • Glucose metabolism
  • Growth factor signaling
  • HIF-1α
  • Hypoxia

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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