TGF-β1 mediates epithelial to mesenchymal transition via the TGF-β/Smad pathway in squamous cell carcinoma of the head and neck

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Abstract

Development of metastasis is a major cause of death for squamous cell carcinoma of the head and neck (SCCHN) patients. Epithelial to mesenchymal transition (EMT) is now regarded as a correlate of tumor metastasis. Given that transforming growth factor-β1 (TGF-β1) is an important inducer of EMT, we examined the effects of TGF-β1 on the human SCCHN cell line Tu686. We found that TGF-β1 mediated cell morphological changes. Phase-contrast microscopy revealed a loss of the adherent phenotype with cellular elongation, decrease in cell-to-cell contact, and the induction of a fibroblast-like state. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that TGF-β1 could induce down-regulation of the epithelial marker E-cadherin and up-regulation of the mesenchymal marker vimentin in Tu686 cells in a concentration- and time-dependent manner. Wound-healing and transwell invasion assay indicated that TGF-β1 promoted Tu686 cell migration and invasion dramatically. In addition, these changes were mediated via canonical TGF-β/Smad signaling with concomitant up-regulation of phosphorylated Smad2. Smad2 RNAi abrogated both expression and functional effects of TGF-β1 on Tu686 cells. In conclusion, the present study demonstrates that TGF-β1 could induce EMT in the SCCHN cell line via the TGF-β/Smad signaling pathway. More importantly, a cell model for EMT was established, which is valuable for future studies on the metastasis of SCCHN. Copyright © 2011 Spandidos Publications Ltd. All rights reserved.

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Yu, C., Liu, Y., Huang, D., Dai, Y., Cai, G., Sun, J., … Zhang, X. (2011). TGF-β1 mediates epithelial to mesenchymal transition via the TGF-β/Smad pathway in squamous cell carcinoma of the head and neck. Oncology Reports, 25(6), 1581–1587. https://doi.org/10.3892/or.2011.1251

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