Title:Metabolic Ink Lactate Modulates Epigenomic Landscape: A Concerted Role of Pro-tumor Microenvironment and Macroenvironment During Carcinogenesis
VOLUME: 21 ISSUE: 3
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, 411033, Cancer and Translational Research Lab, Dr. D.Y. Patil Biotechnology & Bioinformatics Institute, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, 411033
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 years, metabolic-epigenomic reprogramming has been considered
as one of the many tumor hallmarks and it appears to be driven by both microenvironment and
macroenvironment factors including diet, microbiota 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 a lactate
substrate as a metabolic ink for epigenetic writer enzyme that remodels histone proteins. Therefore, preclinical
and clinical attempts are warranted to disrupt the pathway of metabolic-epigenomic reprogramming that will
turn pro-tumor microenvironment into an anti-tumor microenvironment. This paper highlights the metabolicepigenomic
regulation events including lactylation and its metabolic substrate lactate in the tumor
microenvironment.
