Identification of lysine-lactylated substrates in gastric cancer cells

Cancer cells tend to utilize aerobic glycolysis to generate energy and metabolites; the end product of aerobic glycolysis is lactate, which promotes lysine lactylation (Kla). Kla is a newly discovered histone post-translational modification (PTM) that plays important roles in regulating gene expression. However, Kla in non-histone mammalian proteins is unclear. Here, a comprehensive analysis of lactylated proteins in gastric cancer AGS cells was conducted. There were 2375 Kla sites found in 1014 proteins. Interestingly, KEGG pathway analysis showed that these proteins were significantly enriched in spliceosome function. In addition, Kla was more abundant in gastric tumors than in adjacent tissues, and high levels of Kla in gastric tumors were associated with poor prognosis. These results suggest that Kla could be a prognostic marker in gastric cancer. This lysine lactylome analysis in gastric cancer cells, the first of its kind, provides a valuable foundation for further studies of Kla.