A reduced model of cell metabolism to revisit the glycolysis-OXPHOS relationship in the deregulated tumor microenvironment

Cancer cells metabolism focuses the interest of the cancer research community. Although this process is intensely studied experimentally, there are very few theoretical models that address this issue. One of the main reasons is the extraordinary complexity of the metabolism that involves numerous interdependent regulatory networks which makes the computational recreation of this complexity illusory. In this study we propose a reduced model of the metabolism which focuses on the interrelation of the three main energy metabolites which are oxygen, glucose and lactate in order to better understand the dynamics of the core system of the glycolysis-OXPHOS relationship. So simple as it is, the model highlights the main rules allowing the cell to dynamically adapt its metabolism to its changing environment. It also makes it possible to address this impact at the tissue scale. The simulations carried out in a spheroid show non-trivial spatial heterogeneity of energy metabolism. It further suggests that the metabolic features that are commonly attributed to cancer cells are not necessarily due to an intrinsic abnormality of the cells. They can emerge spontaneously due to the deregulated over-acidic environment.

Automated summary

Cancer cells' metabolism is of great interest in cancer research. However, there are few theoretical models addressing this issue due to the complexity of the metabolism. This study proposes a simplified model focusing on the interrelation of three main energy metabolites to better understand the dynamics of the core metabolic system. The model highlights the main rules allowing cells to adapt their metabolism to changing environments and suggests that metabolic features attributed to cancer cells may be due to the deregulated over-acidic environment rather than an intrinsic abnormality of the cells.