EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-\u03b2/SMAD signalling

Liqing Jia,Yanhong Zhou,Wei Xiong,Zheng Li,Gaoming Xiao,Guiyuan Li,Juanjuan Xiang,Linna Chen,Chao Du,Li Fang,Xiaolu Ge

doi:10.1038/s41416-020-01250-4

Abstract

BackgroundEukaryotic 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).MethodsImmunohistochemistry 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).ResultsIn 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.ConclusionsThese findings underscore the molecular functions of EEF1A2 in LUAD metastasis and indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD.

Highlights

Eukaryotic protein translation elongation factor 1α2 (EEF1A2) is an oncogene that promotes the progression of breast and pancreatic cancer
EEF1A2 overexpression in lung adenocarcinoma (LUAD) tissues and cells is strongly correlated with poor prognosis To determine the clinical significance of the EEF1A2 in patients with LUAD, immunohistochemical staining was used to detect EEF1A2 in tissue microarrays (TMAs) consisting of 78 pairs of cancer samples compared with their corresponding adjacent tissues
The area under the receiver operating characteristic (ROC) curve (AUC value) of EEF1A2 for the diagnosis of LUAD was 0.7761. These results suggested that EEF1A2 might be an oncoprotein involved in the progression of LUAD, and an early diagnosis and prognostic factor thereof

Summary

Introduction

Eukaryotic protein translation elongation factor 1α2 (EEF1A2) is an oncogene that promotes the progression of breast and pancreatic cancer. We aimed to elucidate the oncogenic function of EEF1A2 in the metastasis of lung adenocarcinoma (LUAD). 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. 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. NSCLC includes lung adenocarcinoma (LUAD), and squamous cell carcinoma (SCC), which accounts for 80–85% of all lung cancer cases.[2] earlier reports have confirmed the expression characteristics and corresponding therapeutic strategies targeting KRAS, and EGFR mutations, and the EML4-ALK fusion gene in LUAD, the 5-year overall survival rate of lung adenocarcinoma patients remains low at 18%.3–7. An improved understanding of the key underlying metastatic mechanisms of LUAD progression is required

Objectives

Methods

Results

Discussion

Conclusion