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Effect of HGF/c-Met pathway in oral squamous cell carcinoma on EMT and metastatic potential
https://osaka-dent.repo.nii.ac.jp/records/251
https://osaka-dent.repo.nii.ac.jp/records/251a8bf6174-9afb-4112-a912-80930834e9b1
| 名前 / ファイル | ライセンス | アクション |
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学位論文 (510.1 kB)
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論文内容要旨・審査結果要旨 (227.3 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-04-28 | |||||
| 本文言語 | ||||||
| 言語 | eng | |||||
| タイトル | ||||||
| タイトル | Effect of HGF/c-Met pathway in oral squamous cell carcinoma on EMT and metastatic potential | |||||
| 著者 |
木村, 一貴
× 木村, 一貴× Kimura, Kazutaka |
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| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | HGF | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | c-Met | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Oral squamous cell carcinoma | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | SU11274 | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Oral squamous cell carcinoma (OSCC) is characterized by highly invasive tumor cells. Hepatocyte growth factor (HGF) signaling plays an important role in the induction of epithelial-mesenchymal transition (EMT), a process that converts immotile epithelial cells into motile mesenchymal cells and is involved in cancer metastasis by promoting tumor cell scattering. The c-Met, which is a transmembrane tyrosine kinase receptor that may be activated by HGF, which regulates the associated downstream gene expression. This process is important to cell migration in normal and cancerous conditions. This study explored the potential effects of c-Met on HGF-induced EMT in an OSCC cell line. We investigated the function of c-Met in the process of EMT, and its molecular mechanism in oral cancer. OSCC cell line, HSC3 cells, were treated with HGF for varying durations. EMT-associated proteins, including E-cadherin and vimentin, were examined by western blot analysis. The role of c-Met in the mediation of EMT-like changes was investigated using western blot analysis and knockdown by c-Met inhibitor. Moreover, we carried out investigations using immunohistochemical and immunofluorescence staining. We found that treatment with HGF induced EMT-like changes and enhanced the migrative potential of HSC3 cells. Furthermore, HGF-mediated EMT-like changes were associated with c-Met activation, and these changes could be blocked by c-Met knockdown. In particular, immunohistochemical and immunofluorescence staining of c-Met strongry expressed in the invasion front of the tumor cells. This study clearly demonstrated a crucial function for c-Met in EMT development in oral cancer. c-Met-targeted treatment may be an effective therapy for oral cancer. We believe that our data demonstrated that c-Met inhibitor could reduce HGF-induced EMT and cell motility via c-Met blockade and down-regulation of the pro-survival extracellular signal-regulated kinases pathway. |
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| 学位名 | ||||||
| 学位名 | 博士（歯学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 34408 | |||||
| 学位授与機関名 | 大阪歯科大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-03-06 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第868号 | |||||
