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Oral squamous cell carcinoma and cetuximab loop theory

Research Project

Project/Area Number 18K09504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionNiigata University

Principal Investigator

Saeki Makio  新潟大学, 医歯学系, 教授 (30273692)

Co-Investigator(Kenkyū-buntansha) 山崎 学  新潟大学, 医歯学系, 助教 (10547516)
柿原 嘉人  新潟大学, 医歯学系, 助教 (40379938)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsR2TP / p53 / 口腔扁平上皮がん / Reptin / Pontin / ノックアウトマウス / セツキシマブ
Outline of Final Research Achievements

R2TP/PAQosome (particle for arrangement of quaternary structure) is a novel multisubunit chaperone specialized in the assembly/maturation of protein complexes that are involved in essential cellular processes such as PIKKs (phosphatidylinositol 3-kinase-like kinases) signaling, snoRNP (small nucleolar ribonucleoprotein) biogenesis, and RNAP II (RNA polymerase II) complex formation. In this review article, we describe the current understanding of R2TP/PAQosome functions and characteristics as well as how the chaperone complex is involved in oncogenesis, highlighting DNA damage response, mTOR (mammalian target of rapamycin) pathway as well as snoRNP biogenesis. Also, we discuss its possible involvement in HNSCC (head and neck squamous cell carcinoma) including OSCC (oral squamous cell carcinoma). Finally, we provide an overview of current anti-cancer drug development efforts targeting R2TP/PAQosome.

Academic Significance and Societal Importance of the Research Achievements

本研究は、申請者がこれまでに蓄積してきたPontin/Reptinの基礎的な機能解析結果に基づくものである。口腔がんにおいては未だPontin/Reptinの作用機序に関する研究報告例はなかった。申請者はPontin/Reptinが、口腔扁平上皮癌組織の悪性領域で高発現していることを確認し、口腔がんの診断マーカーとなりうることを見出した。Pontin/Reptinは酵母からヒトまでの真核生物において広く保存され、重要な生物学的意味を持つ。これらの基礎的な特性を明らかにすることにより、これまで難治性だった口腔がんはもちろん、他のがん研究への波及効果を含め、他分野へも広く知見を提供できるであろう。

Report

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

    (5 results)

All 2021 2020 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] dentification and characterization of R2TP in the development of oral squamous cell carcinoma2021

    • Author(s)
      Kiguchi T, Kakihara Y, Yamazaki M, Katsura K, Izumi K, Tanuma JI, Saku T, Takagi R, Saeki M.
    • Journal Title

      Biochem Biophys Res Commun .

      Volume: 548 Pages: 161-166

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma2021

    • Author(s)
      Nakamura A et al.
    • Journal Title

      Biochem Biophys Res Commun .

      Volume: 557 Pages: 294-301

    • DOI

      10.1016/j.bbrc.2021.04.021

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] R2TP/PAQosome as a promising chemotherapeutic target in cancer2020

    • Author(s)
      Kakihara Y, Kiguchi T, Ohazama A, Saeki M.
    • Journal Title

      Jpn Dent Sci Rev.

      Volume: 56(1) Issue: 1 Pages: 38-42

    • DOI

      10.1016/j.jdsr.2019.08.001

    • NAID

      50014686606

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Binding of PICK1 PDZ domain with calcineurin B regulates osteoclast differentiation.2018

    • Author(s)
      Kamano Y, Watanabe J, Iida T, Kondo T, Okawa H, Yatani H, Saeki M, Egusa H.
    • Journal Title

      Biochemical and biophysical research communications.

      Volume: 496(1), Issue: 1 Pages: 83-88

    • DOI

      10.1016/j.bbrc.2017.12.173

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Analysis of R2TP complex function in oral squamous cell carcinoma.2018

    • Author(s)
      Kiguchi T, Kakihara Y, Takagi R, Saeki M
    • Organizer
      IADR/PER General Session & Exhibition
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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

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