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Analysis of the roles of linear polyubiquitin chains and Sharpin in hepatocellular carcinoma

Research Project

Project/Area Number 25460981
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

Tateishi Ryosuke  東京大学, 医学部附属病院, 特任講師 (50444089)

Co-Investigator(Kenkyū-buntansha) TANAKA Yasuo  東京大学, 医学部附属病院, 助教 (40422290)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肝臓 / 肝細胞癌 / Sharpin / 癌関連遺伝子 / 浸潤能 / ユビキチン / 直鎖型ポリユビキチン鎖 / SHARPIN
Outline of Final Research Achievements

Sharpin is one of the components of the LUBAC, which specifically generates linear polyubiquitin chains to activate NF-kB pathway. Sharpin is also reported to be up-regulated in various types of cancers including HCC and implicated in cancer progression. In this study, we showed that Sharpin transcription was up-regulated in HCC tissues, and significantly correlated with tumor size and histology. Increased expression of Sharpin enhanced the invasion of hepatoma cells, and cDNA microarray analysis identified that Versican, an extracellular matrix proteoglycan, was also up-regulated in Sharpin expressing cells. Knocking down of Versican greatly attenuated the invasion of hepatoma. Furthermore, Sharpin overexpression resulted in activation of Versican promoter activity. Taken together, these results suggest that Sharpin plays crucial roles in tumor-invasiveness during cancer progression through transactivating Versican.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2016 2015 2014 2013

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Impact of serum ferritin level on hepatocarcinogenesis in chronic hepatitis C patients2015

    • Author(s)
      Uchino K, Tateishi R, Fujiwara N, Minami T, Sato M, Enooku K, Nakagawa H, Asaoka Y, Kondo Y, Yoshida H, Moriya K, Shiina S, Omata M, Koike K.
    • Journal Title

      Hepatol Res.

      Volume: 46 Issue: 4 Pages: 259

    • DOI

      10.1111/hepr.12517

    • URL

      https://pure.teikyo.jp/en/publications/425210f6-eead-4b61-a412-64423208b260

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of improved prognosis between hepatitis B- and hepatitis C-related hepatocellular carcinoma.2015

    • Author(s)
      Minami T, Tateishi R, Shiina S, Nakagomi R, Kondo M, Fujiwara N, Mikami S, Sato M, Uchino K, Enooku K, Nakagawa H, Asaoka Y, Kondo Y, Yoshida H, Koike K.
    • Journal Title

      Hepatol Res.

      Volume: epub Issue: 10

    • DOI

      10.1111/hepr.12468

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of serum levels of interleukin-6 and adiponectin on all-cause, liver-related, and liver-unrelated mortality in chronic hepatitis C patients.2015

    • Author(s)
      Nakagawa H, Fujiwara N, Tateishi R, Arano T, Nakagomi R, Kondo M, Minami T, Sato M, Uchino K, Enooku K, Asaoka Y, Kondo Y, Shiina S, Yoshida H, Koike K.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 30 Issue: 2 Pages: 379-88

    • DOI

      10.1111/jgh.12719

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor markers are more useful in patients undergoing surveillance for hepatocellular carcinoma with unreliable results by ultrasonography2015

    • Author(s)
      Mikami S, Tateishi R, Hagiwara S, Sato M, Minami T, Uchino K, Enooku K, Sato T, Nakagawa H, Masuzaki R, Asaoka Y, Kondo Y, Shiina S, Ikeda H, Omata M, Yoshida H, Koike K.
    • Journal Title

      Hepatol Res.

      Volume: 45 Issue: 4 Pages: 415

    • DOI

      10.1111/hepr.12365

    • URL

      https://localhost/en/publications/f8ebc984-b136-4fe4-bdab-39e29b5f2dae

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study.2015

    • Author(s)
      Tateishi R, Okanoue T, Fujiwara N, Okita K, Kiyosawa K, Omata M, Kumada H, Hayashi N, Koike K.
    • Journal Title

      J Gastroenterol.

      Volume: 50 Issue: 3 Pages: 350-60

    • DOI

      10.1007/s00535-014-0973-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased serum autotaxin levels in hepatocellular carcinoma patients were caused by background liver fibrosis but not by carcinoma2014

    • Author(s)
      Kondo M, Ishizawa T, Enooku K, Tokuhara Y, Ohkawa R, Uranbileg B, Nakagawa H, Tateishi R, Yoshida H, Kokudo N, Koike K, Yatomi Y, Ikeda H
    • Journal Title

      Clin Chim Acta

      Volume: 433C Pages: 128-134

    • DOI

      10.1016/j.cca.2014.03.006

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased Serum Mitochondrial Creatine Kinase Activity as a Risk for Hepatocarcinogenesis in Chronic Hepatitis C Patients.2014

    • Author(s)
      Enooku K, Nakagawa H, Soroida Y, Ohkawa R, Kageyama Y, Uranbileg B, Watanabe N, Tateishi R, Yoshida H, Koike K, Yatomi Y, Ikeda H.
    • Journal Title

      Int J Cancer

      Volume: epub Issue: 4 Pages: 871-879

    • DOI

      10.1002/ijc.28720

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential.2013

    • Author(s)
      Uranbileg B, Enooku K, Soroida Y, Ohkawa R, Kudo Y, Nakagawa H, Tateishi R, Yoshida H, Shinzawa S, Moriya K, Ohtomo N, Nishikawa T, Inoue Y, Tomiya T, Kojima S, Matsuura T, Koike K, Yatomi Y, Ikeda H.
    • Journal Title

      Int J Cancer.

      Volume: 134 Issue: 9 Pages: 2189-98

    • DOI

      10.1002/ijc.28547

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling.2013

    • Author(s)
      He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, Frazer KA, Harismendy O, Hatziapostolou M, Iliopoulos D, Suetsugu A, Hoffman RM, Tateishi R, Koike K, Karin M.
    • Journal Title

      Cell.

      Volume: 155 Issue: 2 Pages: 384-396

    • DOI

      10.1016/j.cell.2013.09.031

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Sharpin cooperates with Wnt pathway to transactivate Versican expression to promote HCC invasion2016

    • Author(s)
      Yasuo Tanaka, Keisuke Tateishi, Takuma Nakatsuka , Yotaro Kudo, Yoshinari Asaoka, Ryosuke Tateishi, Kazuhiko Koike.
    • Organizer
      APASL(Asian Pacific Association for the Study of the Liver) 2016
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都品川区)
    • Year and Date
      2016-02-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規がん遺伝子候補 Sharpinの 肝癌進展における役割の解明2015

    • Author(s)
      田中 康雄、立石 敬介、中塚 拓馬、宮林 弘至、高橋 良太、山本 恵介、工藤 洋太郎、浅岡 良成、伊地知 秀明、建石 良介、小池 和彦
    • Organizer
      日本消化器関連学会機構 JDDW 2015
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都品川区)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Sharpin promotes invasion of hepatocellular carcinoma through trans-activating Versican expressi2014

    • Author(s)
      Yasuo Tanaka, Keisuke Tateishi, Takuma Nakatsuka , Yotaro Kudo, Yoshinari Asaoka, Ryosuke Tateishi, Kazuhiko Koike
    • Organizer
      AASLD 2014 Annual Meeting
    • Place of Presentation
      Boston, USA
    • Year and Date
      2014-11-07 – 2014-11-11
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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