Metabolic Reprogramming and Signaling to Chromatin Modifications in Tumorigenesis

Abstract

Cellular proliferation relies on a high energetic status, replenished through nutrient intake, that leads to the production of biosynthetic material. A communication between the energetic levels and the control of gene expression is essential to engage in cell division. Multiple nutrient and metabolic sensing mechanisms in cells control transcriptional responses through cell signaling cascades that activate specific transcription factors associated with a concomitant regulation of the chromatin state. In addition to this canonical axis, gene expression could be directly influenced by the fluctuation of specific key intermediary metabolites of central metabolic pathways which are also donors or cofactors of histone and DNA modifications. This alternative axis represents a more direct connection between nutrients and the epigenome function. Cancer cells are highly energetically demanding to sustain proliferation. To reach their energetic demands, cancer cells rewire metabolic pathways. Recent discoveries show that perturbations of metabolic pathways in cancer cells have a direct impact on the epigenome. In this chapter, the interaction between metabolic driven changes of transcriptional programs in the context of tumorigenesis will be discussed.