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TBL1XR1 as a potential therapeutic target that promotes epithelial-mesenchymal transition in lung squamous cell
Yuehua Zhao1,2, Hao Lin1,2, Jingwei Jiang1,2
1Department of Oncology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
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.
Insights
Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) promotes lung squamous cell carcinoma (SCC) progression by enhancing cell proliferation, invasion, and migration. TBL1XR1 may be a therapeutic target for lung SCC by influencing epithelial-mesenchymal transition via the TGF-β/Smad pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is implicated in tumor progression, but its role in lung squamous cell carcinoma (SCC) is unclear.
- Understanding TBL1XR1's function in lung SCC is crucial for identifying new therapeutic strategies.
Purpose of the Study:
- To investigate the biological role and molecular mechanisms of TBL1XR1 in lung SCC.
- To determine if TBL1XR1 influences cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) in lung SCC.
Main Methods:
- TBL1XR1 expression was analyzed in lung SCC cell lines.
- In vitro assays (cell counting kit-8, invasion, wound healing) assessed proliferation, invasion, and migration.
- Western blotting examined EMT markers and the transforming growth factor (TGF)-β/mothers against decapentaplegic homolog (Smad) signaling pathway.
Main Results:
- TBL1XR1 was upregulated in lung SCC cells.
- Overexpression of TBL1XR1 enhanced proliferation, invasion, and migration, inducing a mesenchymal phenotype.
- TBL1XR1 modulated EMT markers and the TGF-β/Smad pathway, increasing E-cadherin and decreasing SNAI1, ZEB1, p-Smad2/3, Smad2, and Smad3.
Conclusions:
- TBL1XR1 plays a significant role in lung SCC development and progression.
- TBL1XR1 may promote lung SCC by inducing EMT through activation of the TGF-β/Smad signaling pathway.
- TBL1XR1 represents a potential therapeutic target for lung SCC.
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