title: 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.
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.
authors: 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;
authors: Masafumi
authors: M
authors: Hino
authors: 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.
authors: Masaharu
authors: M
authors: Kamo
authors: 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;
authors: Daishi
authors: D
authors: Saito
authors: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Iwate 028-3694, Japan;
authors: Seiko
authors: S
authors: Kyakumoto
authors: Department of Oral and Maxillofacial Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-shi, Gifu 501-1194, Japan.
authors: Toshiyuki
authors: T
authors: Shibata
authors: 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;
authors: Harumi
authors: H
authors: Mizuki
authors: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Iwate 028-3694, Japan;
authors: Akira
authors: A
authors: Ishisaki
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C435831:WNT5B protein, human; D051153:Wnt Proteins; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10
keywords: MMP-10; Slug; TGF-β; Wnt-5b; invasion