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Oncologie

, Volume 15, Issue 9, pp 435–440 | Cite as

Le métabolisme de la cellule tumorale : l’effet Warburg

  • D. Puyraimond-ZemmourEmail author
  • S. Vignot
Mise au point / Update

Résumé

La prolifération chronique et incontrôlée des cellules cancéreuses n’est pas le résultat unique d’une dérégulation du contrôle moléculaire de la prolifération cellulaire,mais correspond aussi à une adaptation dumétabolisme énergétique à cette nouvelle demande. Alors que les cellules différenciées quiescentes utilisent la fermentation lactique en l’absence d’oxygène et la respiration mitochondriale en présence d’oxygène, les cellules cancéreuses utilisent la fermentation lactique quelles que soient les conditions d’oxygénation. Cette adaptation métabolique irréversible des cellules cancéreuses porte le nom d’effet Warburg. Dans cette revue, nous discuterons de la découverte de l’effet Warburg et argumenterons qu’il n’est pas qu’une simple adaptation à l’hypoxie. En effet, bien qu’une explication consensuelle de ses bénéfices reste un sujet actif de recherche, l’effet Warburg émerge aujourd’hui comme une propriété fondamentale des cancers par son universalité et sonmécanisme de régulationmoléculaire spécifique. Les découvertes récentes dans ce domaine ouvrent aujourd’hui de nouvelles applications cliniques à la fois diagnostiques (TEP-FDG) et thérapeutiques.

Mots clés

EffetWarburg Tumorigenèse Métabolisme Tomographie par émission de positron 

The metabolism of cancer cells: the Warburg effect

Abstract

The sole dysregulation of the cell cycle’s molecular program does not explain the uncontrolled growth of cancer cells. Metabolism adaptation is also required. When differentiated (quiescent) cells depend on lactic fermentation in the absence of oxygen (and mitochondrial respiration when oxygen is present), cancer cells rely on lactic fermentation independently of oxygen availability. This metabolic adaptation is named as the Warburg effect. In this review, we will discuss the initial discovery of the Warburg effect and argue that it is not a simple adaptation to hypoxia. The Warburg effect emerges as a complex phenomenon and is now a hallmark of cancer due to its universality and specific molecular regulation. These recent discoveries open novel avenues for diagnostic and therapeutic interventions.

Keywords

Warburg effect Tumorigenesis Metabolism Positron emission tomography 

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Références

  1. 1.
    Bonnet S, Archer SL, Allalunis-Turner J, et al. (2007) A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11(1): 37–51PubMedCrossRefGoogle Scholar
  2. 2.
    Buzzai M, Jones RG, Amaravadi RK, et al. (2005) The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene 24(26): 4165–4173PubMedCrossRefGoogle Scholar
  3. 3.
    Christofk HR, Vander Heiden MG, Wu N, et al. (2008) Pyruvate-kinase M2 is a phosphotyrosine-binding protein. Nature 452(7184): 181–186PubMedCrossRefGoogle Scholar
  4. 4.
    Christofk HR, Vander Heiden MG, Harris MH, et al. (2008) The M2 splice isoform of pyruvate-kinase is important for cancer metabolism and tumour growth. Nature 452(7184): 230–233PubMedCrossRefGoogle Scholar
  5. 5.
    Czernin J, Phelps ME (2002) Positron emission tomography scanning: current and future applications. Annu Rev Med 53: 89–112PubMedCrossRefGoogle Scholar
  6. 6.
    DeBerardinis RJ, Mancuso A, Daikhin E, et al. (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104(49): 19345–19350PubMedCrossRefGoogle Scholar
  7. 7.
    DeBerardinis RJ, Lum JJ, Hatzivassiliou G, et al. (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7(1): 11–20PubMedCrossRefGoogle Scholar
  8. 8.
    Di Chiro G, DeLaPaz RL, Brooks RA, et al. (1982) Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography. Neurology 32(12): 1323–1329PubMedCrossRefGoogle Scholar
  9. 9.
    Engelman JA, Chen L, Tan X, et al. (2008) Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 14(12): 1351–1356PubMedCrossRefGoogle Scholar
  10. 10.
    Fantin VR, St-Pierre J, Leder P (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9(6): 425–434PubMedCrossRefGoogle Scholar
  11. 11.
    Feron O (2009) Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother Oncol 92(3): 329–333PubMedCrossRefGoogle Scholar
  12. 12.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5): 646–674PubMedCrossRefGoogle Scholar
  13. 13.
    Hsu PP, Sabatini DM (2008) Cancer cell metabolism: Warburg and beyond. Cell 134(5): 703–707PubMedCrossRefGoogle Scholar
  14. 14.
    Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 23(5): 537–548PubMedCrossRefGoogle Scholar
  15. 15.
    Kunkel M, Reichert TE, Benz P, et al. (2003) Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97(4): 1015–1024PubMedCrossRefGoogle Scholar
  16. 16.
    Mochiki E, Kuwano H, Katoh H, et al. (2004) Evaluation of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography for gastric cancer. World J Surg 28(3): 247–253PubMedCrossRefGoogle Scholar
  17. 17.
    Vander-Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930): 1029–1033PubMedCrossRefGoogle Scholar
  18. 18.
    Warburg O (1956) On the origin of cancer cells. Science 123(3191): 309–314PubMedCrossRefGoogle Scholar
  19. 19.
    Warburg O, Wind F, Negelein E (1927) The Metabolism of Tumors in the Body. J Gen Physiol 8(6): 519–530PubMedCrossRefGoogle Scholar
  20. 20.
    Wiesener MS, Münchenhagen PM, Berger I, et al. (2001) Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1alpha in clear cell renal carcinomas. Cancer Res 61(13): 5215–5222PubMedGoogle Scholar

Copyright information

© Springer-Verlag France 2013

Authors and Affiliations

  1. 1.Immunology PhD programHarvard Medical SchoolBostonUSA
  2. 2.Service d’oncologie médicalegroupe hospitalier Pitié-Salpêtrière-Charles-FoixParisFrance

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