p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation

Nat Cell Biol. 2008 May;10(5):611-8. doi: 10.1038/ncb1724. Epub 2008 Apr 6.


Cancer cells use aerobic glycolysis preferentially for energy provision and this metabolic change is important for tumour growth. Here, we have found a link between the tumour suppressor p53, the transcription factor NF-kappaB and glycolysis. In p53-deficient primary cultured cells, kinase activities of IKKalpha and IKKbeta and subsequent NF-kappaB activity were enhanced. Activation of NF-kappaB, by loss of p53, caused an increase in the rate of aerobic glycolysis and upregulation of Glut3. Oncogenic Ras-induced cell transformation and acceleration of aerobic glycolysis in p53-deficient cells were suppressed in the absence of p65/NF-kappaB expression, and were restored by GLUT3 expression. It was also shown that a glycolytic inhibitor diminished the enhanced IKK activity in p53-deficient cells. Moreover, in Ras-expressing p53-deficient cells, IKK activity was suppressed by p65 deficiency and restored by GLUT3 expression. Taken together, these data indicate that p53 restricts activation of the IKK-NF-kappaB pathway through suppression of glycolysis. These results suggest that a positive-feedback loop exists, whereby glycolysis drives IKK-NF-kappaB activation, and that hyperactivation of this loop by loss of p53 is important in oncogene-induced cell transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Genes, ras
  • Glucose / metabolism*
  • Glucose Transporter Type 3 / genetics
  • Glucose Transporter Type 3 / metabolism
  • Glycolysis / physiology
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Lactic Acid / metabolism
  • Mice
  • Mice, Knockout
  • RNA Interference
  • Signal Transduction / physiology
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism


  • Glucose Transporter Type 3
  • Rela protein, mouse
  • Slc2a3 protein, mouse
  • Transcription Factor RelA
  • Tumor Suppressor Protein p53
  • Lactic Acid
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • ras Proteins
  • Glucose