Whole Exome Analysis of EpCAM-positive Hepatocellular Carcinoma Stem Cells

• Project/Area Number: 23590967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: YAMASHITA Taro 金沢大学, 大学病院, 助教 (90377432)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 肝細胞癌 / 癌幹細胞

Research Abstract

Recent evidences suggest that hepatocellular carcinoma possesses cancer stem cells that play a pivotal role on local recurrence and distant organ metastasis after radical treatment. In this study, we evaluated the genetic mutations observed in hepatocellular carcinoma containing EpCAM-positive cancer stem cells at whole exome level. We identified TP53, ARID, and CDKN mutations in EpCAM-positive hepatocellular carcinoma cells. These mutations may be responsible for the maintenance of EpCAM-positive cancer stem cells and therefore may be good targets for eradication of hepatocellular carcinoma.

Research Products

• [Journal Article] The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma (2014)
  • Author(s): Zeng SS, Yamashita T, Kondo M, Nio K, Hayashi T, Hara Y, Nomura Y, Yoshida M, Hayashi T, Oishi N, Ikeda H, Honda M, and Kaneko S
  • Journal Title: J Hepatol Volume: (60) Pages: 127-34
  • NAID: 120005349158
  • Peer Reviewed
• [Journal Article] The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma. (2014)
  • Author(s): Zeng SS, Yamashita T, Kondo M, Nio K, Hayashi T, Hara Y, Nomura Y, Yoshida M, Hayashi T, Oishi N, Ikeda H, Honda M, and Kaneko S.
  • Journal Title: Journal of Hepatology Volume: 60 Issue: 1 Pages: 127-134
  • DOI: 10.1016/j.jhep.2013.08.024
  • NAID: 120005349158
  • Peer Reviewed
• [Journal Article] Discrete Nature of EpCAM+ and CD90+ Cancer Stem Cells in Human Liver Cancer (2013)
  • Author(s): Yamashita T, Honda M, Nakamoto Y, Baba M, Nio K, Hara Y, Zeng SS, Hayashi T, Kondo M, Takatori H, Yamashita T, Mizukoshi E, Ikeda H, Zen Y, Takamura H, Wang XW, and Kaneko S
  • Journal Title: Hepatology Volume: (57) Pages: 1484-97
  • Peer Reviewed
• [Journal Article] Cancer stem cells in the development of liver cancer (2013)
  • Author(s): Yamashita T and Wang XW
  • Journal Title: J Clin Invest Volume: (123) Pages: 1911-8
  • Peer Reviewed
• [Journal Article] Discrete nature of EpCAM(+) and CD90(+) cancer stem cells in human hepatocellular carcinoma. (2013)
  • Author(s): Yamashita T, Nakamoto Y, et al.
  • Journal Title: Hepatology Volume: 57 Issue: 4 Pages: 1484-1497
  • DOI: 10.1002/hep.26168
  • Peer Reviewed
• [Journal Article] Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma (2012)
  • Author(s): Oishi N, Kumar MR, Roessler S, Ji J, Forgues M, Budhu A, Zhao X, Andersen JB, Ye QH, Jia HL, Qin LX, Yamashita T, Woo HG, Kim YJ, Kaneko S, Tang ZY, Thorgeirsson SS, and Wang XW
  • Journal Title: Hepatology Volume: (56) Pages: 1792-803
  • Peer Reviewed
• [Journal Article] Nucleostemin in ijury induced liver regeneration (2012)
  • Author(s): Shugo H, Ooshio T, Naito M, Naka K, Hoshii T, Tadokoro Y, Muraguchi T, Tamase A, Uema N, Yamashita T, Nakamoto Y, Suda T, Kaneko S, and Hirao A
  • Journal Title: Stem Cells Dev Volume: (21) Pages: 3044-54
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of hepatocarcinogenesis in chronic hepatitis C virus infection (2011)
  • Author(s): Yamashita T, Honda M, Kaneko S.
  • Journal Title: J Gastroenterol Hepatol Volume: 26(6) Issue: 6 Pages: 960-4
  • DOI: 10.1111/j.1440-1746.2011.06723.x
  • NAID: 120003141912
  • Peer Reviewed
• [Presentation] Biomarkers of cancer stem cells in HCC (2013)
  • Author(s): Yamashita T, Honda M, Kaneko S
  • Organizer: The 1^<st> International Symposium of Catholic Liver Research Center, Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2013-12-07
• [Presentation] Gd-EOB-DTPA-enhanced MRI and Serum AFP Predict the Prognosis of Early-stage Hepatocellular Carcinoma (2013)
  • Author(s): Yamashita T, Kitao A, Matsui O, Hayashi T, Nio K, Kondo M, Okada H, Yamashita T, Mizukoshi E, Honda M, Nakanuma Y, Takamura H, Ohta T, Nakamoto Y, Yamamoto M, Takayama T, Arii S, Wang XW, and Kaneko S
  • Organizer: AASLD Annual Meeting
  • Place of Presentation: Washington DC
  • Year and Date: 2013-11-05
• [Presentation] The evolution of diverse cancer stem cells in human liver cancer (2013)
  • Author(s): Yamashita T, Honda M, Nio K, Hara Y, Hayashi T, Oishi N, Sunakozaka H, Takatori H, Colombo F, Porretti L, Wang XW, and Kaneko S
  • Organizer: AACR Annual Meeting
  • Place of Presentation: Washington DC
  • Year and Date: 2013-04-07
• [Presentation] Cancer Stem Cells in Hepatocarcinogenesis (2013)
  • Author(s): Yamashita T, Honda M, Kaneko S
  • Organizer: The 2^<nd> JSGE International Topic Conference, Symposium
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 2013-03-22
• [Presentation] The evolution of diverse cancer stem cells in human liver cancer (2012)
  • Author(s): Yamashita T, Honda M, Nakamoto Y, Nio K, Hara Y, Zeng SS, Hayashi T, Yamashita T, Mizukoshi E, Ikeda H, Zen Y, Takamura H, Colombo F, Porretti L, Wang XW, and Kaneko S
  • Organizer: AASLD Annual Meeting
  • Place of Presentation: Boston
  • Year and Date: 2012-11-10
• [Presentation] 肝癌幹細胞形質の多様性と進化 (2012)
  • Author(s): 山下太郎、本多政夫、金子周一
  • Organizer: JDDW2012、シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2012-10-11
• [Presentation] 肝細胞癌の分子分類 (2012)
  • Author(s): 山下太郎、本多政夫、金子周一
  • Organizer: 日本肝癌研究会、教育基調シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2012-07-20
• [Presentation] 肝癌幹細胞の分子標的薬に対する応答性の検討 (2012)
  • Author(s): 山下太郎、本多政夫、金子周一
  • Organizer: 日本肝臓学会総会、ワークショップ
  • Place of Presentation: 金沢
  • Year and Date: 2012-06-08
• [Presentation] Distinct liver cancer stem cells defined by EpCAM and CD90 in human hepatocellular carcinoma (2012)
  • Author(s): Yamashita T, Honda M, Nakamoto Y, Mizukoshi E, Yamashita T, Arai K, Nio K, Hara Y, Wang XW, and Kaneko S
  • Organizer: AACR Annual Meeting
  • Place of Presentation: Chicago
  • Year and Date: 2012-04-04
• [Presentation] The evolution of diverse cancer stem cells in human liver cancer. (2012)
  • Author(s): Yamashita T, Honda M, Nakamoto Y, Nio K, Hara Y, Zeng SS, Hayashi T, Yamashita T, Mizukoshi E, Ikeda H, Zen Y, Takamura H, Colombo F, Porretti L, Wang XW, and Kaneko S.
  • Organizer: American Association of Study of Liver Diseases Annual Meeting
  • Place of Presentation: Hynes Convention Center (U.S.A.)
• [Presentation] 肝癌幹細胞の多様性と進化 (2012)
  • Author(s): 山下太郎、本多政夫、金子周一
  • Organizer: JDDW2012
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] 肝細胞癌の分子分類 (2012)
  • Author(s): 山下太郎、本多政夫、金子周一
  • Organizer: 日本肝癌研究会
  • Place of Presentation: 石川県立音楽堂（石川県）
  • Invited
• [Presentation] Cancer Stem Cells in Hepatocarcinogenesis (2012)
  • Author(s): Taro Yamashita, Masao Honda, and Shuichi Kaneko
  • Organizer: The 10th JSH Single Topic Conference
  • Place of Presentation: 京王プラザホテル（東京都）
  • Invited
• [Presentation] Distinct liver cancer stem cells defined by EpCAM and CD90 in human hepatocellular carcinoma. (2011)
  • Author(s): Yamashita T, Honda M, Nakamoto Y, Mizukoshi E, Yamashita T, Arai K, Nio K, Hara Y, Wang XW, and Kaneko S.
  • Organizer: American Association of Study of Liver Diseases （AASLD）Annual Meeting
  • Place of Presentation: Hynes Convention Center, Boston
• [Presentation] Cancer Stem Cells in Hepatocarcinogenesis. (2011)
  • Author(s): Yamashita T, Honda M, and Kaneko S.
  • Organizer: Asian Pacific Association for the Study of the Liver Single Topic Conference Symposium(招待講演)
  • Place of Presentation: International Convention Center, Jeju
• [Presentation] The evolution of diverse cancer stem cells in human liver cancer.
  • Author(s): Yamashita T, Honda M, Nio K, Hara Y, Hayashi T, Oishi N, Sunakozaka H, Takatori H, Colombo F, Porretti L, Wang XW, and Kaneko S.
  • Organizer: AACR Annual Meeting
  • Place of Presentation: Walter E. Washington Convention Center (Washington DC, U.S.A.)
• [Presentation] Biomarkers of cancer stem cells in HCC.
  • Author(s): Yamashita T, Honda M, Kaneko S.
  • Organizer: The 1st International Symposium of Catholic Liver Research Center
  • Place of Presentation: 1002 hall, Institute of Biomedical Industry, The Catholic University (Seoul, Korea)
  • Invited
• [Presentation] Distinct liver cancer stem cells defined by EpCAM and CD90 in human hepatocellular carcinoma.
  • Author(s): Yamashita T, Honda M, Nakamoto Y, Mizukoshi E, Yamashita T, Arai K, Nio K, Hara Y, Wang XW, and Kaneko S.
  • Organizer: American Association for Cancer Research Annual Meeting
  • Place of Presentation: McCormick Place （U.S.A.）
• [Book] Cancer Stem Cells - The Cutting Edge (2011)
  • Author(s): Yamashita T, Honda M, and Kaneko S.
  • Publisher: InTech