Decoding protein lactylation in the pathogenesis and progression of gynecological cancer

Gynecological tumors represent a significant health burden worldwide. Protein lactylation has emerged as a novel post-translational modification (PTMs) that directly links metabolic reprogramming to epigenetic and functional regulation. Lactylation occurs when lactate covalently modifies the lysine residues of proteins. Initially discovered on histones, lactylation was shown to influence gene transcription; however, accumulating evidence reveals its broader impact on nonhistone proteins, affecting diverse processes. Elevated lactate levels in the tumor microenvironment increase protein lactylation. Evidence suggests a dynamic interplay between tumor metabolism and cancer progression. In this review, we provide an overview of the fundamental aspects of protein lactylation, including the key enzymes that catalyze the addition and removal of lactyl groups. We further emphasize recent discoveries on how lactylation influences the development and progression of gynecological malignancies. Finally, we explore the potential of targeting protein lactylation as an emerging therapeutic strategy in the management of gynecological cancers.