EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling

Br J Cancer. 2021 Mar;124(7):1301-1311. doi: 10.1038/s41416-020-01250-4. Epub 2021 Jan 21.

Abstract

Background: Eukaryotic protein translation elongation factor 1α2 (EEF1A2) is an oncogene that promotes the progression of breast and pancreatic cancer. In this study, we aimed to elucidate the oncogenic function of EEF1A2 in the metastasis of lung adenocarcinoma (LUAD).

Methods: Immunohistochemistry and western blot were used to study EEF1A2 expression levels in LUAD tissues and cells, respectively. The role of EEF1A2 in LUAD progression were investigated in vitro and in vivo. We identified potential EEF1A2-binding proteins by liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. Protein-protein interactions were determined by immunofluorescence and co-immunoprecipitation (Co-IP).

Results: In this study, we report that EEF1A2 mediates the epithelial-mesenchymal transformation (EMT), to promote the metastasis of LUAD cells in vitro and in vivo. Moreover, EEF1A2 interacts with HSP90AB1 to increase TGFβ Receptor (TβR)-I, and TβRII expression, followed by enhanced SMAD3 and pSMAD3 expression and nuclear localisation, which promotes the EMT of LUAD cells. Overexpression of EEF1A2 in cancer tissues is associated with poor prognosis and short survival of patients with LUAD.

Conclusions: These findings underscore the molecular functions of EEF1A2 in LUAD metastasis and indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / secondary*
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Peptide Elongation Factor 1 / genetics
  • Peptide Elongation Factor 1 / metabolism*
  • Prognosis
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*
  • Survival Rate
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • EEF1A2 protein, human
  • HSP90 Heat-Shock Proteins
  • HSP90AB1 protein, human
  • Peptide Elongation Factor 1
  • SMAD3 protein, human
  • Smad3 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1