Year: 2026
Type: article
Abstract: Aspirin (ASA), a classical nonsteroidal anti-inflammatory drug, is known to inhibit glycolysis in cancer cells; however, the underlying mechanism remain incompletely understood. Here, we identify lysine salicylation (Ksa) as an ASA-dependent protein modification that suppresses glycolysis and proliferation in colorectal cancer cells. Specifically, ASA causes Ksa on the key glycolytic enzyme aldolase A (ALDOA), markedly reducing its enzymatic activity without altering protein level. Metabolomic analysis revealed that ASA impairs the conversion of fructose-1,6-bisphosphate (F16BP) to glyceraldehyde-3-phosphate (GAP), thereby disrupting glycolytic flux. In a xenograft mouse model, ASA administration not only inhibited tumor growth but also enhanced ALDOA Ksa level and blocked F16BP-to-GAP conversion. Besides, site-directed mutagenesis and genetic code expansion experiments confirmed that ALDOA K13sa is critical for ASA-mediated inhibition of glycolysis and cancer cell proliferation. Together, this study uncovers Ksa as an innovative mechanism by which ASA affects glycolysis and cancer cell proliferation, providing further insights into its potential role in cancer prevention and therapy.
Source: Acta Pharmaceutica Sinica B
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,600
Funders: National Natural Science Foundation of China, China Postdoctoral Science Foundation, Sichuan University, National Science and Technology Major Project, Sichuan Province Science and Technology Support Program, National Major Science and Technology Projects of China, West China Hospital, Sichuan University
OpenAlex ID: W7167505286