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Mechanosensitive PIEZO channel functions in cancer cells and their pathophysiological significance

Research Project

Project/Area Number 20K07599
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionAichi Gakuin University

Principal Investigator

MURAKI KATSUHIKO  愛知学院大学, 薬学部, 教授 (20254310)

Co-Investigator(Kenkyū-buntansha) 鈴木 裕可  愛知学院大学, 薬学部, 講師 (00581026)
波多野 紀行  愛知学院大学, 薬学部, 講師 (50454319)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsPiezo / 伸展刺激 / 種差 / 分子構造 / がん / PIEZO / cancer cells / mechanosensitive / ion channel
Outline of Research at the Start

機械刺激は、生体内で発生する様々な力圧刺激時に関わる刺激であり、その多様性と応答
反応の解析の困難さから、理解が進んでいない。最近、機械刺激の受容に関わるPIEZOチャ
ネルが同定され、その機能が解明されつつあるが、病態との関わりに関する検討は不十分で
ある。申請者らは、最近、複数のヒトがん細胞において、PIEZOチャネルが機能発現してい
ることを発見した。そこで核心をなす学術的問いとして、「機械刺激は、PIEZOチャネルを
介してがん細胞に何をもたらすのか」を掲げ、本研究課題を実施する。

Outline of Final Research Achievements

Over the course of three years, significant progress has been made in the analysis of Piezo1. Particularly noteworthy is the publication of detailed three-dimensional structural data for Piezo1, enabling the identification of crucial amino acids within the protein based on species variations. This finding holds great significance. Based on this data and the obtained results, a structural domain potentially capable of amplifying tensile stimuli within the structure of gPiezo1 has been discovered and presented at the ICMS conference. On the other hand, the cloning of Piezo2 has not yet been successful, and further efforts are planned to continue this work.

Academic Significance and Societal Importance of the Research Achievements

Piezo1の詳細な3次元構造データが公表され、種差を基にしたPiezo1タンパク中の重要なアミノ酸の同定が可能になった。この構造データと本成果から、gPiezo1の構造中に伸展刺激を増幅する可能性のある構造ドメインを見出した(ICMSで発表)。この領域ががん性疼痛の受容機構に関係するか検討することは、臨床的にも大きな意義があると考えている。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Potent Activation of Human but Not Mouse TRPA1 by JT0102022

    • Author(s)
      M Matsubara, Y Muraki, N Hatano, H Suzuki & K Muraki
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 23 Issue: 22 Pages: 14297-14297

    • DOI

      10.3390/ijms232214297

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients2022

    • Author(s)
      E M Sasso, K Muraki, N Eaton-Fitch P Smith, O L Lesslar, G Deed, S Marshall-Gradisnik
    • Journal Title

      Mol Med

      Volume: 28 Issue: 1 Pages: 98-98

    • DOI

      10.1186/s10020-022-00528-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impaired TRPM3-dependent calcium influx and restoration using Naltrexone in natural killer cells of myalgic encephalomyelitis/chronic fatigue syndrome patients2022

    • Author(s)
      N Eaton-Fitch, S D Preez, H Cabanas, K Muraki, D Staines, S Marshall-Gradisnik
    • Journal Title

      J Trans Med

      Volume: 20 Issue: 1 Pages: 94-94

    • DOI

      10.1186/s12967-022-03297-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Inflammatory Regulation of TRPA1 Expression in Human A549 Lung Epithelial Cells.2021

    • Author(s)
      S Luostarinen, M Hamalainen, N Hatano, K Muraki, E Moilanen
    • Journal Title

      Pulm Pharmacol Ther.

      Volume: 70 Pages: 102059-102059

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential therapeutic benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 ion channels in pathophysiology and treatment.2021

    • Author(s)
      H Cabanas, K Muraki, N Eaton-Fitch, D Staines, S Marshall-Gradisnik.
    • Journal Title

      Frontiers in Immunol.

      Volume: 12 Pages: 687806-687806

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIF-1α dependent upregulation of ZIP8, ZIP14, and TRPA1 modify intracellular Zn2+ accumulation in inflammatory synoviocytes.2021

    • Author(s)
      N Hatano, M Matsubara, H Suzuki, Y Muraki, K Muraki.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 22 Pages: 6349-6349

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Comparison of TRPA1 and PIEZO1 channel functions among species2022

    • Author(s)
      K Muraki
    • Organizer
      Ion Channel Modulation Symposium (ICMS)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] うつ病・不安症に対する扁桃体の関与とその神経基盤-TRPC1/4/5サブファミリーの生理機能と精神疾患への関与2022

    • Author(s)
      村木克彦
    • Organizer
      第14回日本不安症学会学術大会 ランチョンセミナー2
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] PIEZO Channels as a sensor for mechanical stress.2021

    • Author(s)
      K Muraki
    • Organizer
      CFS/ME International 2021: RID - Research Innovation and Discovery Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 薬効解析学

    • URL

      https://www.phar.agu.ac.jp/lab/cell_pharm/cellpharmacol.html

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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