TBL1XR1 as a potential therapeutic target that promotes epithelial‑mesenchymal transition in lung squamous cell carcinoma

Zhao,Yuehua; Lin,Hao; Jiang,Jingwei; Ge,Mengxi; Liang,Xiaohua

doi:10.3892/etm.2018.6955

TBL1XR1 as a potential therapeutic target that promotes epithelial‑mesenchymal transition in lung squamous cell carcinoma

Authors:
- Yuehua Zhao
- Hao Lin
- Jingwei Jiang
- Mengxi Ge
- Xiaohua Liang
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Affiliations: Department of Oncology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
Published online on: November 12, 2018 https://doi.org/10.3892/etm.2018.6955
Pages: 91-98
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transducin (β)‑like 1 X‑linked receptor 1 (TBL1XR1) has been demonstrated to serve a vital role in tumor progression. However, the biological role and molecular mechanisms of TBL1XR1 in lung squamous cell carcinoma (SCC) remain largely unknown. The purpose of the present study was to investigate the biological role of TBL1XR1 and its mechanism in lung SCC. TBL1XR1 was expressed in a human bronchial epithelial cell line and in lung SCC cell lines. The present study analyzed TBL1XR1‑induced proliferation, invasion and migration abilities in vitro using the cell counting kit‑8 assay, cell invasion assay and wound healing assay, respectively. This study examined the effects of TBL1XR1 on epithelial‑mesenchymal transition (EMT) in lung SCC cells and activation of the transforming growth factor (TGF)‑β/mothers against decapentaplegic homolog (Smad) signaling pathway by western blotting. The results indicated that TBL1XR1 was upregulated in lung SCC cells. Overexpression of TBL1XR1 increased the rate of cell proliferation compared with the control group. In vitro, overexpression of TBL1XR1 promoted cell invasion and migration ability compared with the control group. In addition, overexpression of TBL1XR1 produced a mesenchymal phenotype, while cells with downregulated TBL1XR1 produced an epithelial phenotype. Overexpression of TBL1XR1 significantly increased E‑cadherin protein expression whilst snail family transcriptional repressor 1 (SNAI1), zinc finger E‑box binding homebox 1 (ZEB1), p‑Smad2/3, Smad2 and Smad3 protein expression was significantly reduced, compared with the control group. Downregulation of TBL1XR1 produced the opposite results. The present study indicated that TBL1XR1 contributed to lung SCC development and progression, and therefore TBL1XR1 may be a potential therapeutic target. TBL1XR1 may induce EMT of lung SCC cells through activation of the TGF‑β/Smad signaling pathway.

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