Alpha-enolase promotes gastric cancer cell proliferation and metastasis via regulating AKT signaling pathway

Eur J Pharmacol. 2019 Feb 15:845:8-15. doi: 10.1016/j.ejphar.2018.12.035. Epub 2018 Dec 22.

Abstract

Increased aerobic glycolysis is considered as a hallmark of cancer and targeting key glycolytic enzymes will be a promising therapeutic approach in cancer treatment. Alpha-enolase (ENO1), as a prominent glycolytic enzyme, is upregulated in multiple cancers and its overexpression is involved in tumor cell proliferation and metastasis. In the present study, we aimed to investigate the potential role of ENO1 in the development and progression of gastric cancer (GC). Here, we found that ENO1 expression was upregulated in human GC and was associated with Lauren type, lymph node metastasis (LNM) and TNM stage. Knockdown of ENO1 attenuated GC cell proliferation and metastasis and reversed epithelial-mesenchymal transition (EMT) progress in vitro while ENO1 overexpression did the opposite. ENO1 could modulate AKT signaling pathway in GC cells and the enhanced proliferation and migration ability induced by ENO1 overexpression was impaired after incubation with PI3K inhibitor Ly294002 in SGC7901 cells. Our data demonstrated that ENO1 enhances GC cell proliferation and metastasis through the protein kinase B (AKT) signaling pathway, indicating that ENO1/AKT signaling axis may serve as a potential target for treatment of GC.

Keywords: Cancer metabolism; ENO1; Gastric cancer; Metastasis; Proliferation.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / physiology*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Neoplastic
  • Glycolysis
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-akt
  • ENO1 protein, human
  • Phosphopyruvate Hydratase