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.