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J Biochem. 2016 Jun;159(6):631-40. doi: 10.1093/jb/mvw007. Epub 2016 Feb 8.

Transforming growth factor-β1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis.

Author information

1
Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Iwate 028-3694, Japan; Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University, 1-3-27 Chuo-dori, Morioka, Iwate 020-8505, Japan, Japan;
2
Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Iwate 028-3694, Japan; mkamo@iwate-med.ac.jp.
3
Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University, 1-3-27 Chuo-dori, Morioka, Iwate 020-8505, Japan, Japan;
4
Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Iwate 028-3694, Japan;
5
Department of Oral and Maxillofacial Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-shi, Gifu 501-1194, Japan.

Abstract

Molecular mechanism underlying the invasion of oral cancer cells remains to be clarified. We previously demonstrated that transforming growth factor-β1 (TGF-β1) induces the expression of mesenchymal markers in human oral squamous cell carcinoma HSC-4 cells. Intriguingly, the expression of the epithelial-mesenchymal transition-related transcription factor Slug was also significantly upregulated upon TGF-β1 stimulation. However, the mechanism by which Slug transduces the TGF-β1-induced signal to enhance the invasiveness of HSC-4 cells is poorly understood. Proteomic analysis revealed that the expression of matrix metalloproteinase (MMP)-10 was upregulated in TGF-β1-stimulated cells. Additionally, a Boyden chamber assay revealed that the TGF-β1-induced increase in invasiveness of HSC-4 cells was significantly inhibited by MMP-10 small interfering RNA (siRNA). Intriguingly, Slug siRNA suppressed TGF-β1-induced expression of MMP-10. These results suggest that TGF-β1 induces invasion in HSC-4 cells through the upregulation of MMP-10 expression in a Slug-dependent manner. On the other hand, Slug siRNA suppressed TGF-β1-induced Wnt-5b expression. Wnt-5b significantly induced MMP-10 expression, whereas Wnt-5b siRNA suppressed the TGF-β1-induced increase in invasiveness, suggesting that TGF-β1-induced expression of MMP-10 and the resulting upregulation of invasiveness are mediated by Wnt-5b. Overall, these results suggest that TGF-β1 stimulates HSC-4 cell invasion through the Slug/Wnt-5b/MMP-10 signalling axis.

KEYWORDS:

MMP-10; Slug; TGF-β; Wnt-5b; invasion

PMID:
26861993
PMCID:
PMC4892396
DOI:
10.1093/jb/mvw007
[Indexed for MEDLINE]
Free PMC Article

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