TGF‑β1 induces N‑cadherin expression by upregulating Sox9 expression and promoting its nuclear translocation in human oral squamous cell carcinoma cells

Hirano,Taifu; Saito,Daishi; Yamada,Hiroyuki; Ishisaki,Akira; Kamo,Masaharu

doi:10.3892/ol.2020.11582

TGF‑β1 induces N‑cadherin expression by upregulating Sox9 expression and promoting its nuclear translocation in human oral squamous cell carcinoma cells

Authors:
- Taifu Hirano
- Daishi Saito
- Hiroyuki Yamada
- Akira Ishisaki
- Masaharu Kamo
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Affiliations: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba‑cho, Iwate 028‑3694, Japan, Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry, Morioka, Iwate 020‑8505, Japan
Published online on: May 4, 2020 https://doi.org/10.3892/ol.2020.11582
Pages: 474-482
Copyright: © Hirano et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Squamous cell carcinoma (SCC) is the most frequent cancer that develops in the oral cavity. Epithelial‑mesenchymal transition (EMT) is known to play an important role in the process of metastasis of SCC cells. In our previous study, we demonstrated that TGF‑β1 induced EMT in the human oral SCC (hOSCC) cell line HSC‑4. We also found that Slug plays an important role in suppressing E‑cadherin expression and promotion of the migratory activity of HSC‑4 cells. However, we also demonstrated that Slug does not participate in upregulation of N‑cadherin expression, suggesting that EMT‑related transcription factors other than Slug also play an important role in the process. In the present study, we aimed to elucidate how the transcription factor Sox9 affects the TGF‑β1‑induced upregulation of N‑cadherin expression in HSC‑4 cells. We found that TGF‑β1 upregulated Sox9 expression in HSC‑4 cells. In addition, Sox9 siRNA significantly abrogated the TGF‑β1‑induced upregulation of N‑cadherin expression and inhibited the TGF‑β1‑promoted migratory activity in HSC‑4 cells. We also demonstrated that TGF‑β1 upregulated the phosphorylation status of Sox9 and then promoted nuclear translocation of Sox9 from the cytoplasm, possibly resulting in an increase in N‑cadherin expression. The cyclic AMP‑dependent protein kinase A inhibitor H‑89, which is known to suppress phosphorylation of Sox9, significantly abrogated the TGF‑β1‑induced upregulation of N‑cadherin expression. These results suggested that TGF‑β1 induced N‑cadherin expression by upregulating Sox9 expression and promoting its nuclear translocation, which results in EMT progression in hOSCC cells.

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