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
| Autor: | Daishi Saito, Toshiyuki Shibata, Masaharu Kamo, Seiko Kyakumoto, Harumi Mizuki, Akira Ishisaki, Masafumi Hino |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Small interfering RNA Slug Biochemistry Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Matrix Metalloproteinase 10 Cell Line Tumor Humans Neoplasm Invasiveness Molecular Biology Transcription factor biology Mesenchymal stem cell Wnt signaling pathway Regular Papers General Medicine biology.organism_classification Molecular biology Cell biology Neoplasm Proteins Wnt Proteins 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Carcinoma Squamous Cell Mouth Neoplasms Snail Family Transcription Factors Transforming growth factor Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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