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PMID: 15967109 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

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

Neoplasia (New York, N.Y.) ·Vol. 7 ·No. 4 ·2005-04-00 ·Pages 324-30

Robey IF, Lien AD, Welsh SJ, Baggett BK, Gillies RJ

Abstract

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.

MeSH Terms
Blotting, Western Cell Line, Tumor DNA Primers/chemistry Gene Expression Regulation, Neoplastic Glucose/metabolism,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
Chemicals
DNA Primers HIF1A protein, human Hypoxia-Inducible Factor 1, alpha Subunit Lactates Transcription Factors Glucose
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Robey Ian F
Department of Biochemistry and Molecular Biophysics, University of Arizona Cancer Center, Tucson, AZ 85724, USA.
Lien Anthony D
Welsh Sarah J
Baggett Brenda K
Gillies Robert J
References (41)
41 references, click to expand
  1. Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction.
    FEBS Lett. 1999 Oct 29;460(2):251-6 PMID: 10544245
  2. Lineage infidelity of MDA-MB-435 cells: expression of melanocyte proteins in a breast cancer cell line.
    Cancer Res. 2004 May 15;64(10):3479-85 PMID: 15150101
  3. Systematic variation in gene expression patterns in human cancer cell lines.
    Nat Genet. 2000 Mar;24(3):227-35 PMID: 10700174
  4. Causes and effects of heterogeneous perfusion in tumors.
    Neoplasia. 1999 Aug;1(3):197-207 PMID: 10935474
  5. Hypoxia-inducible expression of tumor-associated carbonic anhydrases.
    Cancer Res. 2000 Dec 15;60(24):7075-83 PMID: 11156414
  6. Von Hippel-Lindau tumour suppressor gene is not involved in sporadic human breast cancer.
    Tumour Biol. 2001 May-Jun;22(3):131-6 PMID: 11275790
  7. Microenvironmental and cellular consequences of altered blood flow in tumours.
    Br J Radiol. 2003;76 Spec No 1:S11-22 PMID: 15456710
  8. Tumor-related angiogenesis.
    Crit Rev Oncol Hematol. 1989;9(3):197-242 PMID: 2480145
  9. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.
    N Engl J Med. 1991 Jan 3;324(1):1-8 PMID: 1701519
  10. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation.
    Mol Cell Biol. 1992 Dec;12(12):5447-54 PMID: 1448077
  11. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
    J Biol Chem. 1994 Sep 23;269(38):23757-63 PMID: 8089148
  12. Regulation of erythropoietin production. New insights into molecular mechanisms of oxygen homeostasis.
    Hematol Oncol Clin North Am. 1994 Oct;8(5):863-84 PMID: 7852211
  13. Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia.
    J Biol Chem. 1995 Jun 2;270(22):13333-40 PMID: 7768934
  14. Hypoxia and mitochondrial inhibitors regulate expression of glucose transporter-1 via distinct Cis-acting sequences.
    J Biol Chem. 1995 Dec 8;270(49):29083-9 PMID: 7493931
  15. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.
    Mol Cell Biol. 1996 Sep;16(9):4604-13 PMID: 8756616
  16. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma.
    Cancer Res. 1996 Dec 1;56(23):5522-8 PMID: 8968110
  17. Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia.
    Anticancer Res. 1996 Nov-Dec;16(6B):3459-66 PMID: 9042207
  18. Tumour angiogenesis and prognosis.
    Histopathology. 1997 Mar;30(3):294-301 PMID: 9088964
  19. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth.
    Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8104-9 PMID: 9223322
  20. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.
    Nature. 1998 Jul 30;394(6692):485-90 PMID: 9697772
  21. Hypoxia-inducible factor 1: master regulator of O2 homeostasis.
    Curr Opin Genet Dev. 1998 Oct;8(5):588-94 PMID: 9794818
  22. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.
    Nature. 1999 May 20;399(6733):271-5 PMID: 10353251
  23. On the origin of cancer cells.
    Science. 1956 Feb 24;123(3191):309-14 PMID: 13298683
  24. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.
    Science. 2001 Apr 20;292(5516):464-8 PMID: 11292862
  25. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.
    Science. 2001 Apr 20;292(5516):468-72 PMID: 11292861
  26. A tabulated summary of the FDG PET literature.
    J Nucl Med. 2001 May;42(5 Suppl):1S-93S PMID: 11483694
  27. HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus.
    Cell. 2001 Oct 5;107(1):1-3 PMID: 11595178
  28. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography.
    J Clin Oncol. 2002 Jan 15;20(2):379-87 PMID: 11786564
  29. Positron emission tomography scanning: current and future applications.
    Annu Rev Med. 2002;53:89-112 PMID: 11818465
  30. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis.
    J Biol Chem. 2002 Jun 28;277(26):23111-5 PMID: 11943784
  31. Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway.
    J Biol Chem. 2002 Aug 16;277(33):29936-44 PMID: 12052835
  32. Further evidence to support the melanocytic origin of MDA-MB-435.
    Mol Pathol. 2002 Oct;55(5):294-9 PMID: 12354931
  33. Role of prolyl hydroxylation in oncogenically stabilized hypoxia-inducible factor-1alpha.
    J Biol Chem. 2002 Oct 18;277(42):40112-7 PMID: 12186875
  34. A new mathematical model for relative quantification in real-time RT-PCR.
    Nucleic Acids Res. 2001 May 1;29(9):e45 PMID: 11328886
  35. Activated pp60c-Src leads to elevated hypoxia-inducible factor (HIF)-1alpha expression under normoxia.
    J Biol Chem. 2002 Nov 8;277(45):42919-25 PMID: 12200433
  36. A mathematical model of tumor oxygen and glucose mass transport and metabolism with complex reaction kinetics.
    Radiat Res. 2003 Mar;159(3):336-44 PMID: 12600236
  37. Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism.
    Am J Pathol. 2003 Apr;162(4):1283-91 PMID: 12651620
  38. Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors.
    Neoplasia. 2003 Mar-Apr;5(2):135-45 PMID: 12659686
  39. The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models.
    Cancer Res. 2003 Jul 15;63(14):3847-54 PMID: 12873971
  40. Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha.
    Mol Cancer Ther. 2004 Mar;3(3):233-44 PMID: 15026543
  41. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases.
    Cancer Res. 1999 Nov 15;59(22):5830-5 PMID: 10582706
Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1522-8002
DOI
10.1593/neo.04430
Published
2005-04-00
Pages
324-30
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1501147
Subset
IM
Grants
NCI NIH HHS · R01 CA077575 · United States
NCI NIH HHS · R01-CA77575 · United States
NCI NIH HHS · R01-CA77975-05 · United States
External Links
PubMed source DOI: 10.1593/neo.04430 PMC Full Text
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