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

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

Keiko Kawauchi  1 , Keigo Araki, Kei Tobiume, Nobuyuki Tanaka
Affiliations

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

Keiko Kawauchi et al. Nat Cell Biol. 2008 May.

Abstract

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.

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