Flux variability analysis reveals a tragedy of commons in cancer cells

Abstract

In metabolism processes, enzymes are involved in a cooperative manner of step by step mechanisms trying to guarantee cell survival. Besides, every change in a biological system and its environment within a cell could lead to metabolism alterations due to natural cell response. So, it is reasonable to find metabolism variations within a cell in different conditions. Such enzymes behaviors are very similar to a competitive game where different players try to play for reaching a specific outcome, either by a cooperative or selfish strategy. In this study, we have explored an assumption in which there exists a shift in playing strategy of enzymes from normal to a different biological condition (here cancer) by investigation of pattern alterations in the metabolic subsystem of four cancer cell types (in four cancer stages) using flux calculations and Gene Ontology analysis. Based on the results, we found some metabolic subsystems which contained less flux variation during the cancer progression. The results indicate there might be a game-theoretic strategy in which changing from a beneficial (cooperative) to a selfish strategy happened during cancer stages. It also could be interesting since picking a similar game strategy for all cells would eventually lead the system toward a tragedy of commons (i.e., lower overall fitness for a group or population), in the case of cancer cells, cause the system to be finally disrupted, means death.