  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 reuse lactate, a byproduct 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, whilst 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.
