Beyond Warburg effect--dual metabolic nature of cancer cells

Sci Rep. 2014 May 13;4:4927. doi: 10.1038/srep04927.


Warburg effect is a dominant phenotype of most cancer cells. Here we show that this phenotype depends on its environment. When cancer cells are under regular culture condition, they show Warburg effect; whereas under lactic acidosis, they show a nonglycolytic phenotype, characterized by a high ratio of oxygen consumption rate over glycolytic rate, negligible lactate production and efficient incorporation of glucose carbon(s) into cellular mass. These two metabolic modes are intimately interrelated, for Warburg effect generates lactic acidosis that promotes a transition to a nonglycolytic mode. This dual metabolic nature confers growth advantage to cancer cells adapting to ever changing microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / metabolism*
  • Animals
  • Biological Transport
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Enzymologic
  • Glucose / metabolism
  • Glycolysis
  • Heterografts
  • Humans
  • Hydrogen-Ion Concentration
  • Lactic Acid / metabolism
  • Mice
  • NAD / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Oxygen Consumption
  • Phenotype


  • NAD
  • Lactic Acid
  • Glucose