Keratin 19 as a key molecule in progression of human hepatocellular carcinomas through invasion and angiogenesis.

• Material Type: 博士論文
• Title: Keratin 19 as a key molecule in progression of human hepatocellular carcinomas through invasion and angiogenesis.
• Author/Editor: Takano, Masato; Shimada, Keiji; Fujii, Tomomi; Morita, Kohei; Takeda, Maiko; Nakajima, Yoshiyuki; Nonomura, Akitaka; Konishi, Noboru; Obayashi, Chiho
• Author Heading: Takano, Masato; Shimada, Keiji; Fujii, Tomomi; Morita, Kohei; Takeda, Maiko; Nakajima, Yoshiyuki; Nonomura, Akitaka; Konishi, Noboru; Obayashi, Chiho
• Publication, Distribution, etc.: BioMed Central
• Publication Date: 2016-11-18
• Publication Date (W3CDTF): 2016-11-18
• Alternative Title: 浸潤および血管新生を通しての人肝細胞癌の進行におけるケラチン19分子の役割
• Periodical title: BMC cancer
• No. or year of volume/issue: 16 1
• Volume: 16
• Issue: 1
• Pages: Article No.903-
• ISSN (Periodical Title): ISSN : 1471-2407
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2017-03-15
• Dissertation Number: 乙第1399号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Keratin 19; Hepatocellular carcinoma; Senescence; Apoptosis; Angiogenesis
• Target Audience: 一般
• Note (General): type:Thesis; BACKGROUND: Keratin (K) 19-positive hepatocellular carcinoma (HCC) is well known to have a higher malignant potential than K19-negative HCC: However, the molecular mechanisms involved in K19-mediated progression of HCC remain unclear. We attempted to clarify whether K19 directly affects cell survival and invasiveness in association with cellular senescence or epithelial-mesenchymal transition (EMT) in K19-positive HCC. METHODS: K19 expression was analysed in 136 HCC surgical specimens. The relationship of K19 with clinicopathological factors and survival was analysed. Further, the effect of K19 on cell proliferation, invasion, and angiogenesis was examined by silencing K19 in the human HCC cell lines, HepG2, HuH-7, and PLC/PRF/5. Finally, we investigated HCC invasion, proliferation, and angiogenesis using K19-positive HCC specimens. RESULTS: Analysis of HCC surgical specimens revealed that K19-positive HCC exhibited higher invasiveness, metastatic potential, and poorer prognosis. In vitro experiments using the human HCC cell lines revealed that K19 silencing suppressed cell growth by inducting apoptosis or upregulating p16 and p27, resulting in cellular senescence. In addition, transfection with K19 siRNA upregulated E-cadherin gene expression, significantly inhibited the invasive capacity of the cells, downregulated angiogenesis-related molecules such as vasohibin-1 (VASH1) and fibroblast growth factor 1 (FGFR1), and upregulated vasohibin-2 (VASH2). K19-positive HCC specimens exhibited a high MIB-1 labelling index, decreased E-cadherin expression, and high microvessel density around cancer foci. CONCLUSION: K19 directly promotes cancer cell survival, invasion, and angiogenesis, resulting in HCC progression and poor clinical outcome. K19 may therefore be a novel drug target for the treatment of K19-positive HCC.; 博士（医学）・乙第1399号・平成29年3月15日; © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.; identifier:BMC cancer Vol.16 No.1 Article No.903 (2016 Nov); identifier:14712407; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3332; identifier:BMC cancer, 16(1): Article No.903
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3332/1/01_%e4%b9%991399%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3332/2/02_%e4%b9%991399%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3332/3/03_%e4%b9%991399%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1186/s12885-016-2949-y
• Periodical Title (NCID): AA12034763; https://ci.nii.ac.jp/ncid/AA12034763
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU