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Elucidation of protein networks for the mechanism of carcinogenesis through the oxidoreductase in the endoplasmic reticulum

Research Project

Project/Area Number 18K05329
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
Research InstitutionHokkaido University

Principal Investigator

Nomura Takao  北海道大学, 薬学研究院, 特任助教 (90597840)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords癌 / ミトコンドリア / 機能解明 / 幹細胞 / 小胞体
Outline of Final Research Achievements

There are reports that drug-resistant cell lines were created as cancer stem cells other than primary cultured cells in order to obtain cancer stem cells, but these are just "drug-resistant cells" and are true cancer stem cells. Our research team has succeeded in isolating cancer stem cell-like cells, which are present in very small amounts in commercially available cancer cell lines, by combining multiple methods.
The purpose of this study was to investigate the mechanism of a novel HE-I anticancer drug that targets oxidoreductase localized in the endoplasmic reticulum. Under aerobic conditions, no mitochondrial abnormalities were obtained and similar behavior was observed, however, under anaerobic conditions, susceptibility to HE-I was found to increase. This is considered to prove that HE-I is more effective in vivo than in vitro.

Academic Significance and Societal Importance of the Research Achievements

申請者が開発を続けている抗癌剤は今までの抗癌剤とは標的を別とし、新規作用機序で癌細胞に作用することが考えられる。そのため、既存の癌タンパク質以外で、新たなタンパク質ネットワークが見出されることに期待ができた。以前の研究で見出されたミトコンドリアタンパク質群を本研究では標的としたが、活性酸素種の産生には大きな違いが見出されなかった。しかしながら、嫌気・好気条件ではミトコンドリアによるエネルギー産生には大きな違いがあり、ここに新規抗癌剤の作用機序解明の手がかりが見つかった。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The tetramerization domain of the tree shrew p53 protein displays unique thermostability despite sharing high sequence identity with the human p53 protein2020

    • Author(s)
      Nakagawa Natsumi、Sakaguchi Shuya、Nomura Takao、Kamada Rui、Omichinski James G.、Sakaguchi Kazuyasu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 521 Issue: 3 Pages: 681-686

    • DOI

      10.1016/j.bbrc.2019.10.130

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A copper-deficient form of mutant cu/Zn-superoxide dismutase as an early pathological species in amyotrophic lateral sclerosis2018

    • Author(s)
      Tokuda Eiichi、Nomura Takao、Ohara Shinji、Watanabe Seiji、Yamanaka Koji、Morisaki Yuta、Misawa Hidemi、Furukawa Yoshiaki
    • Journal Title

      Biochimica et Biophysica Acta - Molecular Basis of Disease

      Volume: 印刷中 Issue: 6 Pages: 2119-2130

    • DOI

      10.1016/j.bbadis.2018.03.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells2018

    • Author(s)
      Kakuguchi Wataru、Nomura Takao、Kitamura Tetsuya、Otsuguro Satoko、Matsushita Kazuhiro、Sakaitani Masahiro、Maenaka Katsumi、Tei Kanchu
    • Journal Title

      Cancer Medicine

      Volume: 7 Issue: 12 Pages: 6269-6280

    • DOI

      10.1002/cam4.1877

    • NAID

      120006559018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 小胞体ストレス応答性酸化還元調節酵素を標的とした創薬スクリーニング2019

    • Author(s)
      野村尚生、松丸尊紀、春山知樹、前田直良、奥村正樹、金村進吾、稲葉謙次、田村保明、前仲勝実
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Academia anti-cancer Drug Discovery targeted for ER-stress Responsive Enzyme2019

    • Author(s)
      野村尚生、松丸尊紀、春山知樹、前田直良、奥村正樹、金村進吾、稲葉謙次、田村保明、前仲勝実
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 免疫受容体PILRaと単純ヘルペスウイルス1型gB糖ペプチドの相互作用解析2018

    • Author(s)
      野村尚生、柿田浩輔、古川敦、穴田仁洋、橋下俊一、松永茂樹、齊藤貴士、前仲勝実
    • Organizer
      第13回ケミカルバイオロジー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Binding Mechanism of Glycopeptide Derived from HSV-1 with Human Immune Receptor PILRa2018

    • Author(s)
      野村尚生、柿田浩輔、古川敦、穴田仁洋、橋下俊一、松永茂樹、齊藤貴士、前仲勝実
    • Organizer
      第10回国際ペプチドシンポジウム/第55回ペプチド討論会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト単純ヘルペスウイルス由来糖ペプチドと免疫受容体PILRα相互作用解析2018

    • Author(s)
      野村尚生、柿田浩輔、古川敦、穴田仁洋、橋下俊一、松永茂樹、齊藤貴士、前仲勝実
    • Organizer
      第57回NMR討論会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 初代培養細胞を用いない株化細胞からの癌幹細胞の調製法2020

    • Inventor(s)
      前仲勝実、野村尚生
    • Industrial Property Rights Holder
      前仲勝実、野村尚生
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-097691
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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