Phylogenetic Correlation Between Cellular Metabolism and Oncogenesis

One of the hallmarks of cancer cells is the reprogramming of metabolism, particularly glucose metabolism including glycolysis, TCA cycle, and oxidative phosphorylation (OXPHOS) in order to provide metabolites and energy for their growth and proliferation. Some of the most common oncogenes and tumor suppressors, including TP53, PTEN, PIK3CA, EGFR, and BRAF, are involved in regulation of cancer metabolism. To determine the oncogenic correlates of cancer metabolism, we performed a comprehensive analysis of the phylogenetic profiles of these oncogenes (here called glycolysis-, TCA cycle- and OXPHOS-related or GTO-Oncogenes), other oncogenes not implicated in metabolic reprogramming of cancer cells, and genes involved in glucose metabolism. Phylogenetic profiling of GTO-Oncogenes showed that they could be categorized into 3 subgroups according to their occurrences in different kingdoms and phyla. Subgroup 1, including TP53, was found predominantly in animals. Subgroup 2, including PIK3CA and PTEN, was found in eukaryotes, and Subgroup 3, including EGFR and BRAF, were found in both prokaryotes and eukaryotes. A comparison of the phylogenetic profiling comparison of these oncogenes with those of the glucose metabolism genes demonstrated that TP53 was highly correlated with the subunits of the complexes I, IV, and V of mitochondrial electron transport chain. The phylogenetic profile of PIK3CA displayed high correlation with some components of complexes I, III and IV of the electron transport chain as well as the hexokinase family involved in glycolysis. No significant correlation was observed between phylogenetic profiles of PTEN, EGFR, and BRAF with those of the glucose metabolic genes. In this study, we also predicted the function of other oncogenes in reprogramming of cancer cell metabolism by comparing their phylogenetic profiles with the GTO-Oncogenes profiles. Overall, our results suggest specific evolutionary connections and functional interactions between the process of oncogenic transformation of tumor cells and cellular metabolism.