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.
Highlights
Lung cancer is one of the most common malignant cancers and is the leading cause of cancer-related mortality worldwide [1]
We demonstrated that metastasis-associated protein 1 (MTA1) promotes non-small-cell lung cancer (NSCLC) cell metastasis in vitro and in vivo by encouraging the epithelial to mesenchymal transition (EMT) and activating AKT/ GSK3β/β-catenin signaling
Our results indicated that MTA1 upregulation promoted NSCLC cell migration and invasion, and inhibited cell adhesion
Summary
Lung cancer is one of the most common malignant cancers and is the leading cause of cancer-related mortality worldwide [1]. Epithelial to mesenchymal transition (EMT) is a key step in the invasion and metastasis processes in human cancers [2,3,4]. The molecular mechanisms responsible for non-small cell lung cancer (NSCLC) metastasis are not fully understood. During EMT, epithelial cells lose their epithelial characteristics and assume invasive and migratory mesenchymal phenotypes, enabling them to leave the tissue parenchyma and enter the systemic circulation [4, 5]. EMT is commonly observed in lung cancer cells and may be a potential target for lung cancer therapy [6]. Several inhibitors targeting critical orchestrators at the convergence of EMT pathways are under preclinical and clinical investigation [7]
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