Connections between metabolism and epigenetics: mechanisms and novel anti-cancer strategy

Abstract

Cancer cells undergo metabolic adaptations to sustain their growth and proliferation under several stress conditions thereby displaying metabolic plasticity. Epigenetic modification is known to occur at the DNA, histone, and RNA level, which can alter chromatin state. For almost a century, our focus in cancer biology is dominated by oncogenic mutations. Until recently, the connection between metabolism and epigenetics in a reciprocal manner was spotlighted. Explicitly, several metabolites serve as substrates and co-factors of epigenetic enzymes to carry out post-translational modifications of DNA and histone. Genetic mutations in metabolic enzymes facilitate the production of oncometabolites that ultimately impact epigenetics. Numerous evidences also indicate epigenome is sensitive to cancer metabolism. Conversely, epigenetic dysfunction is certified to alter metabolic enzymes leading to tumorigenesis. Further, the bidirectional relationship between epigenetics and metabolism can impact directly and indirectly on immune microenvironment, which might create a new avenue for drug discovery. Here we summarize the effects of metabolism reprogramming on epigenetic modification, and vice versa; and the latest advances in targeting metabolism-epigenetic crosstalk. We also discuss the principles linking cancer metabolism, epigenetics and immunity, and seek optimal immunotherapy-based combinations.

Inhibition of IDH3α enhanced the efficacy of chemoimmunotherapy by activating cGAS-STING pathway through regulating acidic tumor microenvironments

“…It has been reported in gastric cancer that PKM2 overexpression increases glycolysis to promote gastric cancer cell growth and EMT(Sun et al, 2021). Additionally, 2-HG produced by IDH mutations induces colorectal cancer metastasis and EMT by increasing ZEB1 expression(Chen et al, 2022). In our study, IDH3α acted as a switch from oxidative phosphorylation to aerobic glycolysis, and overexpression IDH3α could increase 2-HG and glycolytic enzyme expression.…”

Abnormal energy metabolism in ALS: a key player?

“…PB is a histone deacetylase (HDAC) inhibitor modulating chromatin state and transcriptional activity [73], while TURSO is a secondary bile acid, also controlling HDAC activity [74]. It is established that epigenetic regulation contributes to cellular metabolic abnormalities in cancer and obesity [75,76]. Fels and collaborators explored this link by treating sporadic ALS fibroblasts with PB-TURSO [77 ▪ ].…”

DNA Methylation: From Cancer Biology to Clinical Perspectives

“…Dysregulated metabolism represents a hallmark of malignancy [72,73]. Recently, accumulating evidence suggests that DNA methylation affects malignant cells' metabolism and vice versa [13]. The metabolic pathways that DNA methylation participates in mainly involve glycolysis, methionine cycle, and tricarboxylic acid (TCA) cycle [74][75][76] (Fig.…”

“…A thorough understanding of the role of DNA methylation in cancer immunity is critical to better navigate epigenetic agents. Further, increasing evidence indicates that DNA methylation affects the alteration of metabolic enzymes, which is directly linked to metabolism reprogramming in oncogenesis [13].…”