Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors.
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-1alpha) overexpression to aggressive cancers, has rekindled an interest in this aspect of tumor metabolism. These studies explore the role of HIF-1alpha 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-1alpha, whereas metastatic cells constitutively express high glycolysis and HIF-1alpha, suggesting that dysregulation of HIF-1alpha may induce the Warburg effect. This hypothesis was tested by renormalizing HIF-1alpha levels in renal carcinoma cells, leading to inhibition of aerobic glycolysis.
Robey
Ian F
IF
Department of Biochemistry and Molecular Biophysics, University of Arizona Cancer Center, Tucson, AZ 85724, USA.
Lien
Anthony D
AD
Welsh
Sarah J
SJ
Baggett
Brenda K
BK
Gillies
Robert J
RJ
D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D006019:Glycolysis; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007773:Lactates / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007773:Lactates; D014157:Transcription Factors; D005947:Glucose