Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the warburg effect

Tomer Shlomi, Tomer Benyamini, Eyal Gottlieb, Roded Sharan, Eytan Ruppin

Research output: Contribution to journalArticlepeer-review

Abstract

The Warburg effect - a classical hallmark of cancer metabolism - is a counter-intuitive phenomenon in which rapidly proliferating cancer cells resort to inefficient ATP production via glycolysis leading to lactate secretion, instead of relying primarily on more efficient energy production through mitochondrial oxidative phosphorylation, as most normal cells do. The causes for the Warburg effect have remained a subject of considerable controversy since its discovery over 80 years ago, with several competing hypotheses. Here, utilizing a genome-scale human metabolic network model accounting for stoichiometric and enzyme solvent capacity considerations, we show that the Warburg effect is a direct consequence of the metabolic adaptation of cancer cells to increase biomass production rate. The analysis is shown to accurately capture a three phase metabolic behavior that is observed experimentally during oncogenic progression, as well as a prominent characteristic of cancer cells involving their preference for glutamine uptake over other amino acids.

Original languageEnglish
Article numbere1002018
JournalPLoS Computational Biology
Volume7
Issue number3
DOIs
StatePublished - Mar 2011

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Modelling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

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