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Review
. 2023 Jun;46(3):465-480.
doi: 10.1007/s13402-023-00775-z. Epub 2023 Jan 19.

Beyond metabolic waste: lysine lactylation and its potential roles in cancer progression and cell fate determination

Jun-Han Wang #  1   2   3 , Ling Mao #  1   2   3 , Jun Wang  1   2   3 , Xiao Zhang  1   2   3 , Min Wu  1   2   3 , Qian Wen  1   2   3 , Shi-Cang Yu  4   5   6
Affiliations
Review

Beyond metabolic waste: lysine lactylation and its potential roles in cancer progression and cell fate determination

Jun-Han Wang et al. Cell Oncol (Dordr). 2023 Jun.

Abstract

Background: Lactate is an important metabolite derived from glycolysis under physiological and pathological conditions. The Warburg effect reveals the vital role of lactate in cancer progression. Numerous studies have reported crucial roles for lactate in cancer progression and cell fate determination. Lactylation, a novel posttranslational modification (PTM), has provided a new opportunity to investigate metabolic epigenetic regulation, and studies of this process have been initiated in a wide range of cancer cells, cancer-associated immune cells, and embryonic stem cells.

Conclusion: Lactylation is a novel and interesting mechanism of lactate metabolism linked to metabolic rewiring and epigenetic remodeling. It is a potential and hopeful target for cancer therapy. Here, we summarize the discovery of lactylation, the mechanisms of site modification, and progress in research on nonhistone lactylation. We focus on the potential roles of lactylation in cancer progression and cell fate determination and the possible therapeutic strategies for targeting lysine lactylation. Finally, we suggest some future research topics on lactylation to inspire some interesting ideas.

Keywords: Lactylation; Posttranslational modification; Somatic cell reprogramming; Tumor microenvironment; Warburg effect.

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