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Identification of phosphoproteins contributing to Epithelial-Mesenchymal Transition.

Research Project

Project/Area Number 17K08648
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKitasato University

Principal Investigator

Shirakihara Takuya  北里大学, 医学部, 講師 (30548756)

Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsEMT / チロシンリン酸化 / リン酸化タンパク質 / チロシンキナーゼ / 癌 / シグナル伝達 / プロテオーム / 発生・分化
Outline of Final Research Achievements

Long-term TGF-β stimulation of epithelial cells induces myofibroblast-like changes (EMyoT), and co-stimulation of TGF-β and FGF-2 enhances EMT (eEMT). Therefore, this study aimed to reveal the phosphorylation signaling pathway involved in the induction of eEMT. Comprehensive shotgun proteomic analysis revealed approximately 250 elevated protein expression in EMyoT and eEMT, respectively, and a combined search using the SILAC method and purification with tyrosine phosphorylation antibodies revealed approximately 800 distinct protein phosphorylations in EMyoT and eEMT. Knockdown of multiple eEMT-specific phosphoproteins did not reveal any change in eEMT inducibility, but inhibitors of Axl suppressed eEMT induction.

Academic Significance and Societal Importance of the Research Achievements

TGF-βとFGF-2の長期曝露によるeEMTは創傷治癒部位や繊維化形成部位、がん微小環境など実際の生体内で誘導されている現象であることが推測できる。それ故、本研究で明らかにしたAxl阻害剤によるeEMT誘導の抑制は、EMTを標的とした治療法開発に繋がる可能性がある。また、SILAC法から新規に同定した123のeEMT特異的なチロシンリン酸化タンパク質の中にも線維化やがんの浸潤・転移促進に重要な未知のシグナル因子が含まれていることが予測される。

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

    (9 results)

All 2022 2021 2019 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Transferrin receptor 1 promotes the fibroblast growth factor receptor-mediated oncogenic potential of diffused-type gastric cancer2022

    • Author(s)
      Shirakihara Takuya、Yamaguchi Hideki、Kondo Tadashi、Yashiro Masakazu、Sakai Ryuichi
    • Journal Title

      Oncogene

      Volume: 41 Issue: 18 Pages: 2587-2596

    • DOI

      10.1038/s41388-022-02270-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] FGFR2遺伝子増幅型スキルス胃がんの進展に対するTfR1の作用機序について2022

    • Author(s)
      白木原琢哉, 堺隆一
    • Organizer
      第31回日本がん転移学会学術集会・総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] The role of TfR1 in the progression of FGFR2 gene-amplified scirrhous gastric cancer2022

    • Author(s)
      白木原琢哉, 堺隆一
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] スキルス胃がんの進展に関わるFGFR2結合タンパク質の機能解析2021

    • Author(s)
      白木原琢哉
    • Organizer
      第30回日本がん転移学会学術集会・総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Functional analysis of FGFR2 binding target protein in scirrhous gastric cancer2021

    • Author(s)
      白木原琢哉
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] スキルス胃がんの進展に関わるFGF受容体結合タンパク質TfR1の機能解析2019

    • Author(s)
      白木原琢哉, 堺隆一
    • Organizer
      第28回日本がん転移学会学術集会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] びまん性胃がんの進展に関わるFGFR2結合タンパク質の探索と機能解析2019

    • Author(s)
      白木原琢哉, 堺隆一
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification and functional analysis of FGFR2 binding proteins in diffuse-type gastric carcinoma2019

    • Author(s)
      Takuya Shirakihara, Ryuichi Sakai
    • Organizer
      American Association for Cancer Research Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effects of FGF signaling on TGF-beta-induced EMT2017

    • Author(s)
      Takuya Shirakihara
    • Organizer
      8th International EMT Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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