| First Author | Lum JJ | Year | 2007 |
| Journal | Genes Dev | Volume | 21 |
| Issue | 9 | Pages | 1037-49 |
| PubMed ID | 17437992 | Mgi Jnum | J:121261 |
| Mgi Id | MGI:3709696 | Doi | 10.1101/gad.1529107 |
| Citation | Lum JJ, et al. (2007) The transcription factor HIF-1{alpha} plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis. Genes Dev 21(9):1037-49 |
| abstractText | 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-1alpha) mRNA. Growth factor-deprived hematopoietic cells do not engage in glucose-dependent anabolic synthesis and neither express Hif-1alpha mRNA nor require HIF-1alpha protein to regulate cell survival in response to hypoxia. However, HIF-1alpha is adaptive for the survival of growth factor-stimulated cells, as suppression of HIF-1alpha results in death when growing cells are exposed to hypoxia. Growth factor-dependent HIF-1alpha 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-1alpha protein is stabilized by hypoxia. Together, these data suggest that HIF-1alpha contributes to the regulation of growth factor-stimulated glucose metabolism even in the absence of hypoxia. |
