4.7 Article

Identification of lysine-lactylated substrates in gastric cancer cells

Journal

ISCIENCE
Volume 25, Issue 7, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2022.104630

Keywords

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Funding

  1. Program of clinical medicine expert team of Suzhou [SZYJTD201824]
  2. Social Development Project of Jiangsu Provincial Science and Technology Department [BE2018698]
  3. Medical engineering cooperation project of Nanjing Municipal Science and Technology Bureau [202110032]

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Cancer cells utilize aerobic glycolysis to promote lysine lactylation, a post-translational modification that plays a crucial role in gene expression regulation. Lactylated proteins are more abundant in gastric tumors and high levels of lysine lactylation are associated with poor prognosis, making it a potential prognostic marker for gastric cancer.
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.

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