Aberrant Metabolism as Inductor of Epigenetic Changes in Breast Cancer: Therapeutic Opportunities

Abstract

Aberrant metabolism is arising interest in the scientific community not only because of the role it plays in the development and establishment of the tumor mass but also the possibility of drug poisoning of key enzymes overexpressed in tumor cells. Moreover, tumor metabolism provides key molecules to maintain the epigenetic changes that are also an undisputed characteristic of each tumor type. This metabolic change includes the Warburg effect and alterations in key pathways involved in glutaminolysis, pentose phosphate, and unsaturated fatty acid biosynthesis. Modifications in all these pathways have consequences that impact genetics and epigenetics processes such as DNA methylation patterns, histone post-translational modifications, triggering oncogenes activation, and loss in tumor suppressor gene expression to lead the tumor establishment. In this review, we describe the metabolic rearrangement and its association with epigenetic regulation in breast cancer, as well as its implication in biological processes involved in cancer progression. A better understanding of these processes could help to find new targets for the diagnosis, prognosis, and treatment of this human health problem.

PTEN‐knockout regulates metabolic rewiring and epigenetic reprogramming in prostate cancer and chemoprevention by triterpenoid ursolic acid

“…Recent research reports that the aberrant metabolism in cancer is not only involved in maintaining a high proliferative rate or survival but also has consequences that impact epigenetic mechanisms such as DNA methylation, histone post‐translational modifications, triggering oncogenes activation or loss of tumor suppressor genes expression resulting in tumor development 53 . In the current study, UA significantly blocked the Pten KO‐regulated pyruvate metabolic metabolites including pyruvate and lactate (Figure 5B) which are highly linked with the basic epigenetic machinery 54,55 . Advances in the understanding of prostate cancer metabolism might help to explain many of the biological responses such as epigenetic modulations that are induced by treatment, which might, in turn, lead to the attainment of more effective therapeutic effects.…”

“…53 In the current study, UA significantly blocked the Pten KO-regulated pyruvate metabolic metabolites including pyruvate and lactate (Figure 5B) which are highly linked with the basic epigenetic machinery. 54,55 Advances in the understanding of prostate cancer metabolism might help to explain many of the biological responses such as epigenetic modulations that are induced by treatment, which might, in turn, lead to the attainment of more effective therapeutic effects.…”

Transcriptional Regulation of Protein Synthesis by Mediator Kinase in MYC-driven Medulloblastoma

“…Another possibility is that changes in translational dysregulation may affect specific molecular or cellular processes that contribute to cancer initiation and progression 66,67 . Studies have demonstrated that aberrant protein synthesis leads to changes in the expression of specific genes by affecting chromatin dynamics via epigenetic mechanisms 68,69 . These findings align with the recognized role of CDK8 in the Mediator complex, suggesting that CDK8 cooperates with MYC or other transcription factors to modulate transcriptional regulation, chromatin modifications, and the overall chromatin landscape, thereby impacting gene expression and crucial cellular processes essential for development, stability, and disease states, such as cancer.…”

Metabolic regulation of endothelial senescence

“…Interestingly, transgenic mice overexpressing G6PDH have been found to exhibit an extended lifespan, which has been attributed to increased NADPH levels. Furthermore, reducing the expression of the tumor suppressor gene ataxia-telangiectasia mutated (ATM) can restore glucose flux throughout the PPP, enabling cells to overcome senescence (174)(175)(176)(177). These studies underscore the significance of the PPP in providing NADPH and maintaining redox balance during cellular senescence.…”