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Identification of GPCR which activates FAK-YAP signaling and promotes castration-resistant growth of prostate cancer

Research Project

Project/Area Number 21K16753
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionChiba University

Principal Investigator

Goto Yusuke  千葉大学, 大学院医学研究院, 助教 (00710576)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords前立腺癌 / 去勢抵抗性増殖 / ムスカリン受容体 / 去勢抵抗性前立腺癌 / 機能性RNA / G蛋白共役型受容体 / Gタンパク共役型受容体 / FAK / YAP
Outline of Research at the Start

本研究では、去勢抵抗性増殖の一因であるFAK-YAPシグナル活性化を来すGPCR探索と、そのシグナル遮断による新規治療の探索を目的とした。特に、最新のゲノム技術とデータベース解析を用いて、網羅的に治療標的分子となり得るGPCR探索を行ない、前立腺癌細胞が、去勢抵抗性増殖機構を獲得する新たなメカニズムを解明したい。

Outline of Final Research Achievements

Small RNA-seq and bioinformatic method showed that miR-15b-5p regulates expression of muscarinic receptor 3 (CHRM3), and that regulation of CHRM3 by miR-15b-5p can inhibit activation of YAP signaling induced by CHRM3. microRNA-15b-5p/m3/YAP signaling axis is a novel pathway which promotes castration-resistant growth of PCa. Our findings provide novel mechanisms of muscarinic-signal-driven CRPC progression.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、miR-15b-5p/CHRM3/YAPシグナルの活性化が前立腺癌の去勢抵抗性増殖の機序の一因と考えられた。前立腺癌の神経依存的な去勢抵抗性増殖がこれまで報告されているが、その原因として、機能性RNAによるムスカリン受容体の遺伝子発現変化が示された。本研究成果は、前立腺癌のアンドロゲン受容体に依存しない去勢抵抗性増殖の機序の解明の一助となりうると考えられた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2023

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

  • [Journal Article] MiR-15b-5p inhibits castration-resistant growth of prostate cancer cells by targeting the muscarinic cholinergic receptor CHRM32023

    • Author(s)
      Shunichi Asai, Yusuke Goto, Kengo Tanigawa, Yuya Tomioka, Mayuko Kato, Keiko Mizuno, Shinichi Sakamoto, Naohiko Seki
    • Journal Title

      FEBS Letter

      Volume: 597 Issue: 8 Pages: 1164

    • DOI

      10.1002/1873-3468.14598

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] microRNA-15b-5p/ Muscarinic receptors/ YAP signaling Contributes to Castration-resistant Growth of Prostate Cancer2023

    • Author(s)
      Yusuke Goto*, Shunichi Asai, Shinichi Sakamoto, Tomokazu Sazuka, Yusuke Imamura, Naohiko Seki, Tomohiko Ichikawa, Chiba, Japan
    • Organizer
      2023年 米国泌尿器科学会年次総会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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