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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423717/pdf/?tool=EBI |
| _version_ | 1828955749266489344 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T07:57:46Z |
| format | Article |
| id | doaj.art-bc857921080949a0a2d8b9b497320061 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-14T07:57:46Z |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-bc857921080949a0a2d8b9b4973200612022-12-21T23:10:31ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-03-0173e100201810.1371/journal.pcbi.1002018Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.Tomer ShlomiTomer BenyaminiEyal GottliebRoded SharanEytan RuppinThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423717/pdf/?tool=EBI |
| spellingShingle | 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. PLoS Computational Biology |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423717/pdf/?tool=EBI |
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