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Elucidation of structure-function relationship of multidrug resistance-associated protein HSPB1 and its clinical application

Research Project

Project/Area Number 17K01955
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomolecular chemistry
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

SAKAI Akiko  大阪医科薬科大学, 医学部, 講師 (30225750)

Co-Investigator(Kenkyū-buntansha) 田中 覚  大阪医科薬科大学, 医学部, 非常勤講師 (50595741)
Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsHSPB1 / 抗癌剤耐性 / HSP1B / オリゴマー構造 / 生体分子 / 熱ショック蛋白質
Outline of Final Research Achievements

We investigated the function of the heat shock protein HSPB1 in the acquisition of resistance to the anticancer drugs 5-fluorouracil and paclitaxel, which have different mechanisms of action. Specifically, we analyzed the phosphorylation and oligomeric structure of HSPB1, as well as the proteins that interact with HSPB1. The results showed that the oligomeric structure and phosphorylation status of HSPB1 were different between sensitive and resistant cells, and that the oligomeric structure and interactions with interacting proteins also differed depending on the anticancer drug.

Academic Significance and Societal Importance of the Research Achievements

多くの癌の治療法として抗癌剤による化学療法が重要であるが、抗癌剤に対する感受性の低下(耐性獲得)が治療上の問題となる。5-FUは大腸癌・乳癌など多くの癌で用いられる抗癌剤であるが、長期・反復投薬によって耐性を獲得する。その機序として5-FUが阻害する核酸代謝酵素の発現亢進が報告されているが、それが観察されない耐性も存在する。本研究の研究成果は耐性獲得機序の解明に貢献すると考えられる。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2022 2020 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Glucose transporter-1 inhibition overcomes imatinib resistance in gastrointestinal stromal tumor cells2022

    • Author(s)
      Shima Takafumi、Taniguchi Kohei、Tokumaru Yoshihisa、Inomata Yosuke、Arima Jun、Lee Sang-Woong、Takabe Kazuaki、Yoshida Kazuhiro、Uchiyama Kazuhisa
    • Journal Title

      Oncology Reports

      Volume: 47 Issue: 1

    • DOI

      10.3892/or.2021.8218

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reaction of threonine synthase with the substrate analogue 2-amino-5-phosphonopentanoate: Implications into the proton transfer at the active site2020

    • Author(s)
      Y. Machida, T. Murakawa, A. Sakai, M. Shoji, Y. Shigeta, H. Hayashi
    • Journal Title

      Biochemistry

      Volume: 167 Issue: 4 Pages: 357-364

    • DOI

      10.1093/jb/mvz100

    • NAID

      40022210984

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A phase II, multicenter, single-arm trial of eribulin as first- or second-line chemotherapy for HER2-negative advanced or metastatic breast cancer: evaluation of efficacy, safety, and patient-reported outcomes2018

    • Author(s)
      Kimura Kosei、Iwamoto Mitsuhiko、Tanaka Satoru、Yamamoto Daigo、Yoshidome Katsuhide、Ogura Hiroyuki、Terasawa Risa、Matsunami Nobuki、Takahashi Yuko、Nitta Toshikatsu、Morimoto Takashi、Fujioka Hiroya、Kawaguchi Kanako、Uchiyama Kazuhisa
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 81 Issue: 5 Pages: 923-933

    • DOI

      10.1007/s00280-018-3567-y

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] トレオニン合成酵素の反応機構―予期せぬアルジミン中間体の出現とその意義2018

    • Author(s)
      町田康博,村川武志,境 晶子,林 秀行
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2024-01-30  

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