Glucose is a primary energy source for cancer cells. Several lines of evidence support the idea that monocarboxylate transporters, such as MCT1, elicit metabolic reprogramming of cancer cells in glucose-poor environments, allowing them to re-use lactate, a by-product of glucose metabolism, as an alternative energy source with serious consequences for disease progression. We employ a synergistic experimental and mathematical modelling approach to explore the evolutionary processes at the root of cancer cell adaptation to glucose deprivation, with particular focus on the mechanisms underlying the increase in MCT1 expression observed in glucose-deprived aggressive cancer cells. Data from in vitro experiments on breast cancer cells are used to inform and calibrate a mathematical model that comprises a partial integro-differential equation for the dynamics of a population of cancer cells structured by the level of MCT1 expression. Analytical and numerical results of this model suggest that environment-induced changes in MCT1 expression mediated by lactate-associated signalling pathways enable a prompt adaptive response of glucose-deprived cancer cells, while fluctuations in MCT1 expression due to epigenetic changes create the substrate for environmental selection to act upon, speeding up the selective sweep underlying cancer cell adaptation to glucose deprivation, and may constitute a long-term bet-hedging mechanism.

Evolutionary dynamics of glucose-deprived cancer cells: insights from experimentally informed mathematical modelling / Almeida, Luis; Denis, Jérôme Alexandre; Ferrand, Nathalie; Lorenzi, Tommaso; Prunet, Antonin; Sabbah, Michéle; Villa, Chiara. - In: JOURNAL OF THE ROYAL SOCIETY INTERFACE. - ISSN 1742-5662. - 21:210(2024). [10.1098/rsif.2023.0587]

Evolutionary dynamics of glucose-deprived cancer cells: insights from experimentally informed mathematical modelling

Lorenzi, Tommaso;
2024

Abstract

Glucose is a primary energy source for cancer cells. Several lines of evidence support the idea that monocarboxylate transporters, such as MCT1, elicit metabolic reprogramming of cancer cells in glucose-poor environments, allowing them to re-use lactate, a by-product of glucose metabolism, as an alternative energy source with serious consequences for disease progression. We employ a synergistic experimental and mathematical modelling approach to explore the evolutionary processes at the root of cancer cell adaptation to glucose deprivation, with particular focus on the mechanisms underlying the increase in MCT1 expression observed in glucose-deprived aggressive cancer cells. Data from in vitro experiments on breast cancer cells are used to inform and calibrate a mathematical model that comprises a partial integro-differential equation for the dynamics of a population of cancer cells structured by the level of MCT1 expression. Analytical and numerical results of this model suggest that environment-induced changes in MCT1 expression mediated by lactate-associated signalling pathways enable a prompt adaptive response of glucose-deprived cancer cells, while fluctuations in MCT1 expression due to epigenetic changes create the substrate for environmental selection to act upon, speeding up the selective sweep underlying cancer cell adaptation to glucose deprivation, and may constitute a long-term bet-hedging mechanism.
File in questo prodotto:
File Dimensione Formato  
2301.08023v3.pdf

accesso aperto

Tipologia: 2. Post-print / Author's Accepted Manuscript
Licenza: Creative commons
Dimensione 4.21 MB
Formato Adobe PDF
4.21 MB Adobe PDF Visualizza/Apri
Evolutionary dynamics of glucose-deprived cancer cells_ insights from experimentally informed mathematical modelling.pdf

non disponibili

Tipologia: 2a Post-print versione editoriale / Version of Record
Licenza: Non Pubblico - Accesso privato/ristretto
Dimensione 877.06 kB
Formato Adobe PDF
877.06 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11583/2986660