The Research Progress of Lactylation in Gastrointestinal Tumors
LI Yongzhao, MI Chen, WANG Dongdong, WANG Wei, ZHANG Yan, YANG Hanteng*
Lactylation, an emerging epigenetic modification, has recently been found to have significant ef fects on the metabolic reprogramming of gastrointestinal tumors and the regulation of the tumor microenvironment. Lactate mediates lactylation modification via its metabolic intermediate lactyl-CoA. This novel post-translational mod ification mechanism regulates the conformation and functionality of both histones and non-histone proteins through the specific conjugation of lactate moieties to lysine residues, thereby demonstrating critical associations with gene expression regulation, tumor progression (including growth, invasion, metastasis), immune evasion, and chemoresis tance.This review systematically summarizes the molecular mechanisms of lactate metabolism and lactylation, as well as their biological functions and clinical significance in gastrointestinal cancers such as gastric cancer, colorectal can cer, and liver cancer. The article also discusses therapeutic strategies targeting lactate and lactylation, including inhibi tion of lactate metabolism pathways, intervention in lactylation modifications, and novel directions for combination therapy. Despite the challenges in studying the molecular mechanisms of lactylation and developing targeted drugs, research on lactylation as a potential therapeutic target shows great promise and provides new insights into the precise diagnosis, treatment, and overcoming chemotherapy resistance in gastrointestinal tumors.
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