Molecular mechanism of transforming growth factor-β1-induced cell migration and invasion of HSC-4 human squamous cell carcinoma cells

• Masaharu KAMO

  Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University

• Daishi SAITO

  Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University

• Masafumi HINO

  Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University

• Takahiro CHIBA

  Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University

• Hiroyuki YAMADA

  Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University

• Akira ISHISAKI

  Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University

Bibliographic Information

Other Title

• ヒト口腔扁平上皮癌細胞HSC-4 における細胞遊走・浸潤能に 関与するTGF-β1 誘導性上皮間葉転換の分子機構

Abstract

The underlying molecular mechanism of oral cancer invasion is not apparent. In this review, we explain the molecular mechanism for the epithelial-mesenchymal transition （EMT） and EMT-related cell migration and invasion by TGF-β in human oral squamous cell carcinoma （hOSCC）cells. We examined whether TGF-β-induced EMT of hOSCC cells, and cell migration and invasive potential. Among six kinds of hOSCC cells, HSC-4 cells responded to TGF-β1 the most from the upregulations of Smad2 phosphorylation and the expression of target genes against TGF-β. The expression of Slug, which is an EMT-related transcription factor, was increased by TGF-β1 stimulation. The expression suppression of Slug by RNA interference inhibited the expression of the mesenchymal marker and the cell migration of the HSC-4 cells. The expressions of binding proteins for integrin α3β1, which activates the focal adhesion kinase （FAK） to relay signals for the promotion of migratory activity, were increased by TGF-β1 stimulation. Thus, EMT and cell migration through the integrin α3β1/FAK pathway were upregulated by TGF-β1-induced Slug. On the other hand, the expression of matrix metalloproteinase-10 （MMP-10） was increased by TGF-β1 stimulation, and the invasive potential was inhibited by MMP-10 siRNA. Slug siRNA suppressed the expression of MMP-10, indicating that the invasion of HSC-4 cells was induced through Slug-dependent upregulation of MMP-10 expression by TGF-β1 stimulation. In addition, Slug siRNA suppressed Wnt-5b expression. Wnt-5b stimulation upregulated MMP-10 expression in HSC-4 cells. Moreover, Wnt-5b siRNA suppressed invasive potential and MMP-10 expression in HSC-4 cells. Consequently, TGF-β1 induced the migratory activity and invasive ability of hOSCCs by Slug/α3β1/FAK and Slug/Wnt-5b/MMP-10 signal transduction systems, respectively.

Journal

• Dental Journal of Iwate Medical University

  Dental Journal of Iwate Medical University 43 (2), 107-121, 2018-10-18

  The Dental Society of Iwate Medical University

Keywords

• epithelial-mesenchymal transition
• invasion
• squamous cell carcinoma
• Slug
• Wnt

Details

• CRID: 1390283659850194944
• NII Article ID: 130007795904
• DOI: 10.20663/iwateshigakukaishi.43.2_107
• ISSN: 24241822
• ISSN: 03851311
• Web Site: http://id.nii.ac.jp/1181/00009810/
• Web Site: https://search.jamas.or.jp/link/ui/2019037212
• Text Lang: ja
• Data Source:
  • JaLC
  • IRDB
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed