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Analysis of mTORC1-FOXK1 axis in lifestyle-related diseases

Research Project

Project/Area Number 18K06962
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionNagoya City University

Principal Investigator

NAKATSUMI Hirokazu  名古屋市立大学, 医薬学総合研究院(薬学), 講師 (20596837)

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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsmTORC1 / 脂肪肝 / 糖尿病 / 生活習慣病 / 肝疾患 / 慢性炎症 / FOXK1
Outline of Final Research Achievements

There are two similarities between lifestyle-related diseases and cancer. The first point is that they are in a chronic inflammatory state, and the second point is that abnormal activation of mTORC1 is observed. Based on these similarities, we hypothesized that the transcription factor FOXK1, which is activated downstream of mTORC1, promotes both of lifestyle-related diseases and cancer. We identified that FOXK1 deficient mice were improved fatty liver-related inflammation, fibrosis, and tumorigenesis.

Academic Significance and Societal Importance of the Research Achievements

生活習慣病、特に非アルコール性脂肪性肝炎の患者数は増加傾向にあり、アルコール性・ウイルス性肝炎が減少傾向にあることと対照的である。治療法の確立は急務であるが、現在は減量を基本とした治療法以外は存在しない。本研究では、非アルコール性脂肪性肝炎の新たな治療ターゲットとしてFOXK1を見出した。FOXK1を標的とした薬剤の開発は脂肪肝と関連する炎症、線維症、および腫瘍形成を抑制する可能性がある。

Report

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

    (10 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (6 results) (of which Invited: 3 results)

  • [Journal Article] Skp2 contributes to cell cycle progression in trophoblast stem cells and to placental development.2020

    • Author(s)
      Yamauchi, Y., Nita, A., Nishiyama, M., Muto, Y., Shimizu, H., Nakatsumi, H., Nakayama, K. I.
    • Journal Title

      Genes Cells

      Volume: XX Issue: 6 Pages: 427-438

    • DOI

      10.1111/gtc.12769

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation2020

    • Author(s)
      Shirane Michiko、Wada Mariko、Morita Keiko、Hayashi Nahoki、Kunimatsu Reina、Matsumoto Yuki、Matsuzaki Fumiko、Nakatsumi Hirokazu、Ohta Keisuke、Tamura Yasushi、Nakayama Keiichi I.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 4576-4576

    • DOI

      10.1038/s41467-020-18413-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells2019

    • Author(s)
      Shimizu Hideyuki、Takeishi Shoichiro、Nakatsumi Hirokazu、Nakayama Keiichi I.
    • Journal Title

      JCI Insight

      Volume: 4 Issue: 4

    • DOI

      10.1172/jci.insight.125138

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear-cytoplasmic shuttling protein PP2AB56 contributes to mTORC1-dependent dephosphorylation of FOXK12018

    • Author(s)
      Nakatsumi Hirokazu、Oka Takeru、Higa Tsunaki、Shirane Michiko、Nakayama Keiichi I.
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 7 Pages: 599-605

    • DOI

      10.1111/gtc.12597

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 定量的リン酸化プロテオミクスによるmTOR下流の大規模シグナル解析2020

    • Author(s)
      中津海洋一
    • Organizer
      第1回シロリムス新作用研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 定量的リン酸化プロテオミクスによるmTORC1下流の新規がん促進シグナルの解析2019

    • Author(s)
      中津海 洋一・松本 雅記・白根 道子・中山 敬一
    • Organizer
      日本プロテオーム学会2019年大会
    • Related Report
      2019 Research-status Report
  • [Presentation] PP2AB56 は核内転写因子FOXK1 のmTORC1 依存的脱リン酸化に寄与する2019

    • Author(s)
      中津海 洋一・白根 道子・中山 敬一
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 定量的大規模リン酸化プロテオミクスによるmTORC1下流のシグナル解析2019

    • Author(s)
      中津海 洋一
    • Organizer
      基礎生物学研究所 部門公開セミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] mTORC1依存的な転写因子の脱リン酸化メカニズムとその生物学的意義2018

    • Author(s)
      中津海 洋一
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages.2018

    • Author(s)
      中津海 洋一
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report

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

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