糖酵解重编程与乳酸化串扰在肿瘤中的研究进展OA

Metabolic reprogramming is a hallmark of cancer,with the Warburg effect-driven aerobic glycolysis leading to a substantial accumulation of lactate in the tumor microenvironment.For a long time,lactate was considered a mere metabolic end product;however,recent studies have found that it acts as an important signaling molecule,profoundly influenc-ing tumor progression by inducing a novel post-translational modification-lactylation.Lactylation,driven by lactate,occurs on both histones and non-histone proteins and is finely regulated by the'writer''eraser'and'reader'mechanisms,thereby altering the function of target proteins and gene expression.This review systematically explores the bidirectional regulatory network between glycolytic reprogramming and lactylation:on one hand,key glycolytic regulators promote lactate production,thereby increasing lactylation levels;on the other hand,lactylation can feedback to regulate the activity and expression of key glycolytic enzymes,forming a pro-tumor positive feedback loop.This interaction plays a central role in tumor proliferation,metastasis,DNA damage repair,and immune evasion.Consequently,targeting lactate production,lactate transport,or the lactylation process itself has emerged as a highly promising anti-cancer strategy and shows potential synergy with existing therapies such as immune checkpoint inhibitors.In-depth analysis of the glycolysis-lactylation axis will provide a crucial theoretical basis for developing novel cancer treatment approaches.