High intratumoral expression of eIF4A1 promotes epithelial-to-mesenchymal transition and predicts unfavorable prognosis in gastric cancer

Acta Biochim Biophys Sin (Shanghai). 2020 Mar 18;52(3):310-319. doi: 10.1093/abbs/gmz168.

Abstract

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer-related death worldwide. Aberrant protein translation contributes to the oncogenesis and development of cancers, and upregulation of translation initiation factor eIF4A1 has been observed in several kinds of malignancies. However, the role of eIF4A1 in gastric cancer progression remains unclear. In this study, we found that the expression of eIF4A1, a component of translation initiation complex, was increased in gastric cancer. High expression of eIF4A1 was positively associated with poor tumor differentiation, late T stage, lymph node metastasis, advanced TNM stage, and poor prognosis in patients with gastric cancer. Overexpression of eIF4A1 promoted the migration and invasion of gastric cancer cells in vitro and enhanced tumor metastasis in nude mice model. Mechanism studies revealed that eIF4A1 induced epithelial-to-mesenchymal transition (EMT) of gastric cancer cells through driving the translation of SNAI1 mRNA. Together, these findings indicate that eIF4A1 promotes EMT and metastasis of gastric cancer and suggest that eIF4A1 is a potential target for the adjuvant therapy for gastric cancer patients.

Keywords: eIF4A1; epithelial-to-mesenchymal transition; gastric cancer; prognostic factor.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Eukaryotic Initiation Factor-4A / genetics*
  • Eukaryotic Initiation Factor-4A / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • EIF4A1 protein, human
  • Eukaryotic Initiation Factor-4A