ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism

Nat Chem Biol. 2023 Dec;19(12):1492-1503. doi: 10.1038/s41589-023-01391-6. Epub 2023 Jul 27.


Enolase 1 (ENO1) is a glycolytic enzyme that plays essential roles in various pathological activities including cancer development. However, the mechanisms underlying ENO1-contributed tumorigenesis are not well explained. Here, we uncover that ENO1, as an RNA-binding protein, binds to the cytosine-uracil-guanine-rich elements of YAP1 messenger RNA to promote its translation. ENO1 and YAP1 positively regulate alternative arachidonic acid (AA) metabolism by inverse regulation of PLCB1 and HPGD (15-hydroxyprostaglandin dehydrogenase). The YAP1/PLCB1/HPGD axis-mediated activation of AA metabolism and subsequent accumulation of prostaglandin E2 (PGE2) are responsible for ENO1-mediated cancer progression, which can be retarded by aspirin. Finally, aberrant activation of ENO1/YAP1/PLCB1 and decreased HPGD expression in clinical hepatocellular carcinoma samples indicate a potential correlation between ENO1-regulated AA metabolism and cancer development. These findings underline a new function of ENO1 in regulating AA metabolism and tumorigenesis, suggesting a therapeutic potential for aspirin in patients with liver cancer with aberrant expression of ENO1 or YAP1.

MeSH terms

  • Arachidonic Acid
  • Aspirin / pharmacology
  • Biomarkers, Tumor
  • Carcinogenesis* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / metabolism
  • Tumor Suppressor Proteins / genetics


  • Arachidonic Acid
  • Phosphopyruvate Hydratase
  • Aspirin
  • ENO1 protein, human
  • DNA-Binding Proteins
  • Biomarkers, Tumor
  • Tumor Suppressor Proteins