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

Neoplasia. 2005 Apr;7(4):324-30. doi: 10.1593/neo.04430.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • DNA Primers / chemistry
  • Gene Expression Regulation, Neoplastic*
  • Glucose / metabolism
  • Glucose / pharmacokinetics
  • Glycolysis*
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lactates / metabolism
  • Neoplasms / metabolism
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factors / metabolism*


  • DNA Primers
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lactates
  • Transcription Factors
  • Glucose