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

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 mito...

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Autores principales:	Tomer Shlomi, Tomer Benyamini, Eyal Gottlieb, Roded Sharan, Eytan Ruppin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bc857921080949a0a2d8b9b497320061
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spelling	oai:doaj.org-article:bc857921080949a0a2d8b9b4973200612021-11-18T05:50:39ZGenome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.1553-734X1553-735810.1371/journal.pcbi.1002018https://doaj.org/article/bc857921080949a0a2d8b9b4973200612011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423717/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The 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.Tomer ShlomiTomer BenyaminiEyal GottliebRoded SharanEytan RuppinPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 3, p e1002018 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Tomer Shlomi Tomer Benyamini Eyal Gottlieb Roded Sharan Eytan Ruppin Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.
description	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.
format	article
author	Tomer Shlomi Tomer Benyamini Eyal Gottlieb Roded Sharan Eytan Ruppin
author_facet	Tomer Shlomi Tomer Benyamini Eyal Gottlieb Roded Sharan Eytan Ruppin
author_sort	Tomer Shlomi
title	Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.
title_short	Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.
title_full	Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.
title_fullStr	Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.
title_full_unstemmed	Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.
title_sort	genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the warburg effect.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/bc857921080949a0a2d8b9b497320061
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Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.

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