Hypoxia-inducible factor-1α and the glycolytic phenotype in tumors

Metastatic tumors generally exhibit aerobic glycolysis (the Warburg effect). The advent of [F-18]fluorodeoxyglucose positron emission tomography imaging, coupled with recent findings linking hypoxia-inducible factor (HIF-1 alpha) overexpression to aggressive cancers, has rekindled an interest in this aspect of tumor metabolism. These studies explore the role of HIF-1 alpha in human breast cancer lines and its relationship to glycolytic regulation. Here we demonstrate that, under normal oxygen conditions, nonmetastatic cells consume less glucose and express low HIF-1 alpha, whereas metastatic cells constitutively express high glycolysis and HIF-1 alpha, suggesting that dysregulation of HIF-1 alpha may induce the Warburg effect. This hypothesis was tested by renormalizing HIF-1 alpha levels in renal carcinoma cells, leading to inhibition of aerobic glycolysis.