MTA1 promotes epithelial to mesenchymal transition and metastasis in non-small-cell lung cancer

// Ke Ma 1, * , Yangwei Fan 1, * , Xuyuan Dong 1 , Danfeng Dong 1 , Yuyan Guo 2 , Xin Wei 3 , Jing Ning 4 , Qianqian Geng 5 , Chuying Wang 1 , Yuan Hu 1 , Mengya Li 1 , Wenxia Niu 1 , Enxiao Li 1 and Yinying Wu 1 1 Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, P.R. China 2 Department of Medical Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, P.R. China 3 Department of Medical Oncology, Shaanxi Province People’s Hospital, Xi’an, Shaanxi 710068, P.R. China 4 Department of Obstetrics and Gynecology, Xi’an Third Hospital, Xi’an, Shaanxi 710068, P.R. China 5 Department of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, P.R. China * These authors have contributed equally to this work Correspondence to: Yinying Wu, email: shadowless_111@163.com , makeyfly@126.com Enxiao Li, email: doclienxiao@sina.com Keywords: MTA1, metastasis, epithelial to mesenchymal transition, NSCLC, AKT Received: August 10, 2016 Accepted: February 27, 2017 Published: March 21, 2017 ABSTRACT The present study assessed the role of metastasis-associated protein 1 (MTA1) in epithelial to mesenchymal transition (EMT) and metastasis in non-small-cell lung cancer (NSCLC) cells using a normal lung epithelium cell line, three NSCLC cell lines, a mouse NSCLC model, and 56 clinical NSCLC samples. We observed that MTA1 overexpression decreased cellular adhesion, promoted migration and invasion, and changed cytoskeletal polarity. MTA1 knockdown had the opposite effects. MTA1 overexpression decreased E-cadherin, Claudin-1, and ZO-1 levels and increased Vimentin expression in vitro and in vivo , through activation of AKT/GSK3β/β-catenin signaling. However, treatment with the AKT inhibitor MK2206 did not completely rescue effects associated with MTA1 expression changes, indicating that pathways other than the AKT/GSK3β/β-catenin pathway could be involved in MTA1-induced EMT. Compared with normal lung tissues, MTA1 expression was elevated in NSCLC patient tissues and was correlated with American Joint Committee on Cancer stage, T stage, lymphatic metastasis, and patient overall survival. Additionally, MTA1 expression was positively associated with p-AKT and cytoplasmic β-catenin levels. These findings indicate MTA1 promotes NSCLC cell EMT and metastasis via AKT/GSK3β/β-catenin signaling, which suggests MTA1 may be an effective anti-NSCLC therapeutic target.