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

• Published in: British journal of cancer 2021-03, Vol.124 (7), p.1301-1311
• Main Authors: Jia, Liqing, Ge, Xiaolu, Du, Chao, Chen, Linna, Zhou, Yanhong, Xiong, Wei, Xiang, Juanjuan, Li, Guiyuan, Xiao, Gaoming, Fang, Li, Li, Zheng
• Format: Article
• Language: English
• Subjects: 631/67/395; 631/80/86; Adenocarcinoma; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - secondary; Animals; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cell Proliferation; Drug Resistance; Epidemiology; Female; Gene Expression Regulation, Neoplastic; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Humans; Immunofluorescence; Immunohistochemistry; Immunoprecipitation; Liquid chromatography; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mass spectroscopy; Medical prognosis; Mesenchyme; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Medicine; Oncology; Pancreatic cancer; Peptide Elongation Factor 1 - genetics; Peptide Elongation Factor 1 - metabolism; Prognosis; Protein interaction; Proteins; Smad protein; Smad3 protein; Smad3 Protein - genetics; Smad3 Protein - metabolism; Survival Rate; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Translation elongation; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-01250-4

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.