EEF1D overexpression promotes osteosarcoma cell proliferation by facilitating Akt-mTOR and Akt-bad signaling

J Exp Clin Cancer Res. 2018 Mar 6;37(1):50. doi: 10.1186/s13046-018-0715-5.

Abstract

Background: Dysregulation of eukaryotic translation elongation factor 1 delta (EEF1D) in cancers has been reported; however, the role and mechanisms of EEF1D in osteosarcoma remain poorly understood. The aim of this study is to investigate the expression and role of EEF1D in osteosarcoma and to elucidate its underlying mechanisms.

Methods: The expression of EEF1D in osteosarcomas and cell lines was evaluated by qRT-PCR, Western blotting and immunohistochemistry. EEF1D knockdown using small interfering RNA (siRNA) was employed to analyze the role of EEF1D in osteosarcoma cell proliferation and cell cycle progression. The host signaling pathways affected by EEF1D knockdown were detected using PathScan® intracellular signaling array kit.

Results: The expression of EEF1D was found to be up-regulated in human osteosarcoma tissues and cell lines. Its expression was positively correlated with Enneking stage and the tumor recurrence. EEF1D knockdown inhibited osteosarcoma cell proliferation, colony-forming ability, and cell cycle G2/M transition in vitro. In addition, EEF1D knockdown decreased the levels of phospho-Akt, phospho-mTOR, and phospho-Bad proteins.

Conclusions: EEF1D is upregulated in osteosarcoma and plays a tumor promoting role by facilitating Akt-mTOR and Akt-Bad signaling pathways. Accordingly, EEF1D is a potential target for cancer therapy.

Keywords: Akt-bad signaling pathway; Akt-mTOR signaling pathway; EEF1D; Osteosarcoma; Proliferation.

MeSH terms

  • Adolescent
  • Adult
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Child
  • Female
  • Gene Expression*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Peptide Elongation Factor 1 / genetics*
  • Peptide Elongation Factor 1 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Recurrence
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Young Adult

Substances

  • EEF1D protein, human
  • Peptide Elongation Factor 1
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases