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

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

British journal of cancer 2021 Mar

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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). 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). 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. 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.

Citation

Liqing Jia, Xiaolu Ge, Chao Du, Linna Chen, Yanhong Zhou, Wei Xiong, Juanjuan Xiang, Guiyuan Li, Gaoming Xiao, Li Fang, Zheng Li. EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling. British journal of cancer. 2021 Mar;124(7):1301-1311