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

Shlomi, T., Benyamini, T., Gottlieb, E. , Sharan, R. and Ruppin, E. (2011) Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect. PLoS Computational Biology, 7(3), e1002018. (doi: 10.1371/journal.pcbi.1002018)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pcbi.1002018

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

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gottlieb, Professor Eyal
Authors: Shlomi, T., Benyamini, T., Gottlieb, E., Sharan, R., and Ruppin, E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:PLoS Computational Biology
Publisher:Public Library of Science
ISSN:1553-734X
ISSN (Online):1553-7358
Copyright Holders:Copyright © 2011 The Authors
First Published:First published in PLoS Computational Biology 7(3):e1002018
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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