Eukaryotic elongation factors 2 promotes tumor cell proliferation and correlates with poor prognosis in ovarian cancer

Tissue Cell. 2018 Aug:53:53-60. doi: 10.1016/j.tice.2018.05.014. Epub 2018 May 30.

Abstract

Eukaryotic elongation factors 2 (eEF2) plays an essential role in the GTP-dependent translocation of the ribosome along mRNA. Previous studies have shown that eEF2 is overexpressed in various tumors. However, little is known about the role of eEF2 in ovarian cancer. The aim of the present study is to examine the effect of eEF2 on ovarian cancer proliferation. We first measured eEF2 protein expression by western blot using six fresh ovarian cancer tissues from G1 to G3. The results showed that eEF2 expression gradually increased from G1 to G3. Additionally, eEF2 expression correlated significantly with grade (P = 0.045), FIGO stage (P = 0.035) and Ki67 (P < 0.05). Additionally, there was a significant positive association between eEF2 expression and Ki67 (r = 0.855). Cox's proportional hazards model also showed that eEF2 (P = 0.004) and Ki67 (P < 0.001) were an independent prognostic factor of overall survival in ovarian cancer patients. In vitro, after the release of ovarian cancer cell line (HO8910) from serum starvation, the expression of eEF2, cyclinD1 and PCNA was up-regulated. Moreover, silencing eEF2 in HO8910 cells decreased cell proliferation. Finally, we hypothesize that eEF2 may be activated in a positive feedback cycle through inactivation of eEF2K via the PI3K/Akt/mTOR pathway. These data provide novel insights into developing experimental therapies for ovarian cancer.

Keywords: Ovarian cancer; Proliferation; eEF2.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Peptide Elongation Factor 2 / metabolism*
  • Prognosis
  • Signal Transduction*

Substances

  • Neoplasm Proteins
  • Peptide Elongation Factor 2