Evolutionary dynamics of the Warburg effect: Glycolysis as a collective action problem among cancer cells

Archetti, Marco (2014) Evolutionary dynamics of the Warburg effect: Glycolysis as a collective action problem among cancer cells. Journal of Theoretical Biology, 341. pp. 1-8. ISSN 0022-5193

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The upregulation of glycolysis in cancer cells (the “Warburg effect”) is common and has implications for prognosis and treatment. As it is energetically inefficient under adequate oxygen supply, its adaptive value for a tumor remains unclear. It has been suggested that the acidity produced by glycolysis is beneficial for cancer cells because it promotes proliferation against normal cells. Current models of this acid-mediated tumor invasion hypothesis, however, do not account for increased glycolysis under non-limiting oxygen concentrations and therefore do not fully explain the Warburg effect. Here I show that the Warburg effect can be explained as a form of cooperation among cancer cells, in which the products of glycolysis act as a public good, even when oxygen supply is high enough to make glycolysis energetically inefficient. A multiplayer game with non-linear, non-monotonic payoff functions that models the benefits of the acidity induced by glycolysis reveals that clonal selection can stabilize glycolysis even when energetically costly, that is, under non-limiting oxygen concentration. Characterizing the evolutionary dynamics of glycolysis reveals cases in which anti-cancer therapies that rely on the modification of acidity can be effective.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Organisms and the Environment
Depositing User: Pure Connector
Date Deposited: 06 Jan 2014 14:12
Last Modified: 04 Mar 2024 16:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/46883
DOI: 10.1016/j.jtbi.2013.09.017

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