Metabolic Ink Lactate Modulates Epigenomic Landscape: A Concerted Role of Pro-tumor Microenvironment and Macroenvironment During Carcinogenesis

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Author(s): Nilesh Kumar Sharma*, Jayanta K. Pal

Journal Name: Current Molecular Medicine

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Abstract:

Tumor heterogeneity is influenced by various factors including genetic, epigenetic and axis of metabolic-epigenomic regulation. In recent, metabolic-epigenomic reprogramming is considered as one of many tumor hallmarks and it appears to be driven by both microenvironment and macroenvironment factors including diet, microbiotas and environmental pressures. Epigenetically, histone lysine residues are altered by various post-translational modifications (PTMs) such as acetylation, acylation, methylation and lactylation. Furthermore, lactylation is suggested as a new form of PTM that uses lactate substrate as a metabolic ink for epigenetic writer enzyme that remodel histone proteins. Therefore, preclinical and clinical attempts are warranted to disrupt pathway of metabolic-epigenomic reprogramming that will turn pro-tumor microenvironment into antitumor microenvironment. This paper highlights the metabolic-epigenomic regulation events including lactylation and its metabolic substrate lactate in tumor microenvironment.

Keywords: Metabolite, epigenomic, cancer, microenvironment, diet, lactate

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