Recent progress in cancer metabolism research has identified lactylation as a critical post-translational modification influencing tumor development and progression. The process relies on lactate accumulation and the activation of lactate-sensitive acyltransferases. Beyond its role in epigenetic regulation, lactylation has emerged as a significant factor in tumor metabolism and evolution, offering fresh opportunities for developing targeted therapies that transcend traditional approaches. This review explores the growing importance of lactylation in cancer biology and highlights its potential for advancing diagnostic tools and therapeutic strategies.
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http://dx.doi.org/10.1038/s41420-025-02349-4 | DOI Listing |
Cell Commun Signal
March 2025
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, No. 56, Xinjiannan Road, Ying Ze District, Taiyuan, 030001, China.
Lactate, once considered a mere byproduct of anaerobic metabolism, is now recognized as a critical signaling molecule with diverse roles in physiology and pathology. There are two stereoisomers of lactate: L- and D-lactate. Recent studies have shown that disruptions in these two lactate stereoisomers have distinct effects on health and disease.
View Article and Find Full Text PDFMol Cell
March 2025
Department of Experimental and Clinical Biomedical Sciences "Mario Serio, " University of Florence, Viale Morgagni 50, 50134 Florence, Italy. Electronic address:
The recently discovered lysine lactylation represents a critical post-translational modification with widespread implications in epigenetics and cancer biology. Initially identified on histones, lysine lactylation has been also described on non-histone proteins, playing a pivotal role in transcriptional activation, protein function, and cellular processes. Two major sources of the lactyl moiety have been currently distinguished: L-lactyl-CoA (precursor of the L-lactyl moiety) and S-D-lactylglutathione (precursor of the D-lactyl moiety), which enable enzymatic and non-enzymatic mechanisms of lysine lactylation, respectively.
View Article and Find Full Text PDFImmunity
March 2025
College of Medicine and Health, University of Birmingham, Birmingham, UK. Electronic address:
Lactate, the end product of both anaerobic and aerobic glycolysis in proliferating and growing cells-with the latter process known as the Warburg effect-is historically considered a mere waste product of cell and tissue metabolism. However, research over the past ten years has unveiled multifaceted functions of lactate that critically shape and impact cellular biology. Beyond serving as a fuel source, lactate is now known to influence gene expression through histone modification and to function as a signaling molecule that impacts a wide range of cellular activities.
View Article and Find Full Text PDFFunct Integr Genomics
March 2025
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Osteosarcoma is the most common bone tumor and a highly aggressive malignant neoplasm. This study aims to elucidate the role of lactylation-related genes (LRGs) in osteosarcoma, with the goal of improving prognostic accuracy and enhancing the efficacy of immunotherapy. Using public datasets, we integrated differential and correlated genes based on single-cell sequencing AUCell scores and performed enrichment analysis and risk model construction on these genes.
View Article and Find Full Text PDFInt Immunopharmacol
March 2025
Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:
T cells play an important role in adaptive immune responses, providing antigen specificity for pathogen and tumor recognition. Recent studies have elucidated the complex interplay between T cell metabolism and broad epigenetic modifications in response to tumors, occurring at transcriptional, post-transcriptional, and post-translational levels. At the transcriptional level, gene expression is regulated through mechanisms such as DNA methylation, chromatin remodeling, and transcription factor activity.
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