Metabolic Reprogramming and Signaling to Chromatin Modifications in Tumorigenesis
- 203 Downloads
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.
KeywordsEpigenetics Intermediary metabolism Chromatin.
- Badur MG, Muthusamy T, Parker SJ et al (2018) Oncogenic R132 IDH1 mutations limit NADPH for De Novo lipogenesis through (D)2-hydroxyglutarate production in fibrosarcoma cells graphical abstract highlights d D2HG production competes with reductive biosynthesis for NADPH in IDH1-mutant cells d 2 H trac. Cell Rep 25. https://doi.org/10.1016/j.celrep.2018.09.074PubMedCrossRefPubMedCentralGoogle Scholar
- Dehennaut V, Leprince D, Lefebvre T, Hansen U (2014b) O-GlcNAcylation, an epigenetic mark. Focus on the histone code, TET family proteins, and polycomb group proteins. Front Endocrinol. https://doi.org/10.3389/fendo.2014.00155
- Poirier LA, Wise CK, Delongchamp RR, Sinha R (2001) Blood determinations of S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine: correlations with diet. Cancer Epidemiol Biomark Prev 10:649–655Google Scholar
- Potapova IA, El-Maghrabi MR, Doronin SV, Benjamin WB (2000) Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of atp:citrate lyase by phosphorylated sugars. Biochemistry. https://doi.org/10.1021/bi992159yPubMedCrossRefGoogle Scholar