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Hypoxia-Inducible Factor-1α and the Glycolytic Phenotype in Tumors1

By Ian F Robey, Anthony D Lien, Sarah J Welsh, Brenda K Baggett and Robert J Gillies


Metastatic tumors generally exhibit aerobic glycolysis (the Warburg effect). The advent of [18F]fluorodeoxyglucose positron emission tomography imaging, coupled with recent findings linking hypoxia-inducible factor (HIF-1α) overexpression to aggressive cancers, has rekindled an interest in this aspect of tumor metabolism. These studies explore the role of HIF-1α 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-1α, whereas metastatic cells constitutively express high glycolysis and HIF-1α, suggesting that dysregulation of HIF-1α may induce the Warburg effect. This hypothesis was tested by renormalizing HIF-1α levels in renal carcinoma cells, leading to inhibition of aerobic glycolysis

Topics: Research Article
Publisher: Neoplasia Press Inc.
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Provided by: PubMed Central
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