Metabolism and Transcription in Cancer: Merging Two Classic Tales

Abstract

Cellular plasticity, or the ability of a cancer cell to adapt to changes in the microenvironment, is a major determinant of cell survival and functionality that require the coordination of transcriptional programs with signaling and metabolic pathways. In this scenario, these pathways sense and integrate nutrient signals for the induction of coordinated gene expression programs in cancer. This minireview focuses on recent advances that shed light on the bidirectional relationship between metabolism and gene transcription, and their biological outcomes in cancer. Specifically, we will discuss how metabolic changes occurring in cancer cells impact on gene expression, both at the level of the epigenetic landscape and transcription factor regulation.

Keywords: DNA and histone methylation; cancer metabolism; gene expression regulation; histone acetylation; nutrient sensing networks; transcription factors.

Figure 1

Transcription and metabolic programs as potential tool for precision medicine. (A) The application of the precision medicine concept will depend on the selection of specific cancer therapies based on both transcriptional and metabolic programs of cancer patients. (B) Mechanistic basis of precision medicine. Bidirectional interplay between transcription and metabolic programs. T, transcription programs; M, metabolic programs. Each color exemplifies different programs.

Figure 2

Schematic representation of the complex relationship between metabolism and gene expression. Metabolic perturbations, as a result of environmental, mutational and metabolic insults, directly impact on gene expression programs, both at the level of epigenetic changes and transcriptional activities. The final outcome is that the conjunction of metabolism and transcription have a profound impact on oncogenesis.