GLUT1 production in cancer cells: a tragedy of the commons.
Journal
NPJ systems biology and applications
ISSN: 2056-7189
Titre abrégé: NPJ Syst Biol Appl
Pays: England
ID NLM: 101677786
Informations de publication
Date de publication:
29 06 2022
29 06 2022
Historique:
received:
08
06
2021
accepted:
31
05
2022
entrez:
29
6
2022
pubmed:
30
6
2022
medline:
2
7
2022
Statut:
epublish
Résumé
The tragedy of the commons occurs when competition among individual members of a group leads to overexploitation of a shared resource to the detriment of the overall population. We hypothesize that cancer cells may engage in a tragedy of the commons when competing for a shared resource such as glucose. To formalize this notion, we create a game theoretic model of glucose uptake based on a cell's investment in transporters relative to that of its neighboring cells. We show that production of transporters per cell increases as the number of competing cells in a microenvironment increases and nutrient uptake per cell decreases. Furthermore, the greater the resource availability, the more intense the tragedy of the commons at the ESS. Based on our simulations, cancer cells produce 2.2-2.7 times more glucose transporters than would produce optimal fitness for all group members. A tragedy of the commons affords novel therapeutic strategies. By simulating GLUT1 inhibitor and glucose deprivation treatments, we demonstrate a synergistic combination with standard-of-care therapies, while also displaying the existence of a trade-off between competition among cancer cells and depression of their gain function. Assuming cancer cell transporter production is heritable, we then show the potential for a sucker's gambit therapy by exploiting this trade-off. By strategically changing environmental conditions, we can take advantage of cellular competition and gain function depression.
Identifiants
pubmed: 35768428
doi: 10.1038/s41540-022-00229-6
pii: 10.1038/s41540-022-00229-6
pmc: PMC9243083
doi:
Substances chimiques
Glucose Transporter Type 1
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
22Subventions
Organisme : NCI NIH HHS
ID : R01 CA258089
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA193489
Pays : United States
Informations de copyright
© 2022. The Author(s).
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