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Elucidation of the role of organelle stress response in oral cancer stem cells

Research Project

Project/Area Number 18H02973
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionUniversity of Miyazaki

Principal Investigator

Nishitoh Hideki  宮崎大学, 医学部, 教授 (00332627)

Co-Investigator(Kenkyū-buntansha) 泰江 章博  徳島大学, 病院, 講師 (80380046)
高雄 啓三  富山大学, 研究推進機構 研究推進総合支援センター, 教授 (80420397)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords小胞体ストレス / ストレス応答 / 口腔がん / 小胞体 / ミトコンドリア / がん幹細胞
Outline of Final Research Achievements

The cancer stem cell hypothesis is one of the factors that lead to highly malignant transformation of cancer that prevents its cure. Elucidation of the mechanisms of cancer stem cells is expected to lead to the development of next-generation molecularly targeted therapeutics. In this study, we aimed to elucidate the role of organelle stress response in stem cell proliferation and differentiation, and furthermore, to differentiate cancer stem cells into less invasive and less metastatic cancers through its regulation. We investigated the involvement of organelle stress response signaling in stem cells and revealed the importance of endoplasmic reticulum quality control for stem cell proliferation and differentiation. The results of this study are expected to be a new molecular target for cancer therapy.

Academic Significance and Societal Importance of the Research Achievements

がん細胞の生存と不均質性獲得に関連性が高いといわれる、小胞体やミトコンドリアから発信されるストレス応答は、がん幹細胞の維持と悪性化にどのように関与するか全く不明であった。このことについて明らかにすることを目的とした本研究は、申請者らが有するこれまでのオルガネラ研究から得られた知見と実験技術に基づいたものであり、その独自性と目的達成の可能性は高く、そこから得られる成果は、将来の口腔がん根治に向けた応用研究へと創造性が高いと期待された。今後は、がん治療の新たな治療戦略、および分子マーカーとして応用研究が進むことが期待される。

Report

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

    (16 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] 褐色脂肪細胞の熱産生とエネルギー代謝2021

    • Author(s)
      西頭英起
    • Journal Title

      臨床免疫・アレルギー科 科学評論社

      Volume: 75 Pages: 226-226

    • Related Report
      2020 Annual Research Report
  • [Journal Article] ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue.2020

    • Author(s)
      Kato H, Okabe K, Miyake M, Hattori K, Fukaya T, Tanimoto K, Beini S, Mizuguchi M, Torii S, Arakawa S, Ono M, Saito Y, Sugiyama T, Funatsu T, Sato K, Shimizu S, Oyadomari S, Ichijo H, Kadowaki H, Nishitoh H.
    • Journal Title

      Life science alliance

      Volume: 3 Issue: 3 Pages: 201900576-201900576

    • DOI

      10.26508/lsa.201900576

    • NAID

      120006980545

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monitoring lipid droplet dynamics in living cells by using fluorescent probes2019

    • Author(s)
      Tatenaka Y, Kato H, Ishiyama M, Sasamoto K, Shiga M, Nishitoh H, Ueno Y
    • Journal Title

      Biochemistry

      Volume: 12 Issue: 6 Pages: 499-503

    • DOI

      10.1021/acs.biochem.8b01071

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endoplasmic reticulum quality control by garbage disposal.2019

    • Author(s)
      Kadowaki H, Nishitoh H
    • Journal Title

      The FEBS Journal

      Volume: 286 Issue: 2 Pages: 232-240

    • DOI

      10.1111/febs.14589

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paradigm shift from ‘Compartment’ to ‘Zone’ in the understanding of organelles2018

    • Author(s)
      Nishitoh Hideki
    • Journal Title

      The Journal of Biochemistry

      Volume: 165 Issue: 2 Pages: 97-99

    • DOI

      10.1093/jb/mvy107

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanism of ER stress-induced pre-emptive quality control involving association of the translocon, Derlin-1, and HRD12018

    • Author(s)
      Kadowaki H, Satrimafitrah P, Takami Y, Nishitoh H
    • Journal Title

      Scientific Reports

      Volume: ー Issue: 1 Pages: 7317-7317

    • DOI

      10.1038/s41598-018-25724-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ER-resident sensor PERK-mediated regulation of mitochondrial function in brown adipose tissue2021

    • Author(s)
      門脇寿枝、西頭英起
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Regulation of brown adipocyte function through the crosstalk signaling between mitochondria and the ER2019

    • Author(s)
      Hideki Nishitoh
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] PERK is essential for mitochondrial thermogenesis in brown adipose tissue2019

    • Author(s)
      Hironori Kato and Hideki Nishitoh
    • Organizer
      EMBO Workshop Proteostasis: From organelles to organisms
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Crosstalk signaling between mitochondria and endoplasmic reticulum is essential for brown adipocyte function2018

    • Author(s)
      西頭英起
    • Organizer
      Keystone Symposia conference “Mitochondrial Biology”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Crosstalk signaling between mitochondria and endoplasmic reticulum is essential for brown adipocyte function2018

    • Author(s)
      Hideki Nishitoh
    • Organizer
      Cell Symposia “Multifaceted Mitochondria”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Translational regulation of newly synthesized protein in ER stress-induced pre-emptive quality control2018

    • Author(s)
      西頭英起、門脇寿枝
    • Organizer
      International Symposium on “Proteins; from the Cradle to the Grave”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Unconventional PERK signaling regulates mitochondrial function in brown adipocytes2018

    • Author(s)
      加藤裕紀、西頭英起
    • Organizer
      EMBO Workshop“Endoplasmic reticulum function in health and disease”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of newly synthesized protein degradation in ER stress-induced pre-emptive quality control2018

    • Author(s)
      門脇寿枝、西頭英起
    • Organizer
      EMBO Workshop “Endoplasmic reticulum function in health and disease”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] オルガネラから発信されるシグナルによる生体の機能制御2018

    • Author(s)
      西頭英起
    • Organizer
      第13回臨床ストレス応答学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] プローブ、ミトコンドリアの状態判定用キット、ミトコンドリアの状態判定方法及びミトコンドリア機能改善剤のスクリーニング方法2018

    • Inventor(s)
      西頭英起、加藤裕紀
    • Industrial Property Rights Holder
      西頭英起、加藤裕紀
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-234295
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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

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