Title:Metabolic Ink Lactate Modulates Epigenomic Landscape: A Concerted Role of Pro-tumor Microenvironment and Macroenvironment During Carcinogenesis
VOLUME: 20
Author(s):Nilesh Kumar Sharma* and Jayanta K. Pal
Affiliation:Cancer and Translational Research Lab, Dr. D.Y. Patil Biotechnology & Bioinformatics Institute, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, Cancer and Translational Research Lab, Dr. D.Y. Patil Biotechnology & Bioinformatics Institute, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra
Keywords: Metabolite, epigenomic, cancer, microenvironment, diet, lactate
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.
