Dual roles of lactylation modification in gastric cancer: Crosstalk between metabolic reprogramming and epigenetic regulation (Review).

Source: PubMed, NCBI / U.S. National Library of Medicine

Gastric cancer (GC) is among the most prevalent malignant tumors worldwide, and its occurrence and progression are closely associated with metabolic abnormalities and remodeling of the tumor microenvironment. As an emerging metabolism‑related post‑translational modification, lactylation acts as a central hub connecting metabolic reprogramming and epigenetic regulation in tumor cells. The present review systematically describes the reprogramming features of lactate metabolism in the GC microenvironment; dissects the enzymatic system and molecular characteristics of lactylation; and reveals a bidirectional positive feedback loop in which histone H3 lysine 18 lactylation (H3K18la) promotes lactate production by upregulating glycolytic genes, and lactate accumulation, in turn, enhances H3K18la levels. A three‑dimensional regulatory network of 'metabolic reprogramming‑epigenetic regulation‑immune microenvironment remodeling' is thereby established in GC. The present review also reveals the clinical value of lactylation as a prognostic biomarker for GC, proposes combination therapeutic strategies targeting lactylation, and provides a theoretical basis and translational direction for the precise diagnosis and treatment of GC.