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Elucidation of molecular mechanisms of tumor initiation and progression by ribosomal stresses

Research Project

Project/Area Number 18K15211
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKobe University

Principal Investigator

Otani Junji  神戸大学, 医学研究科, 助教 (10770878)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsHippo経路 / 核小体ストレス
Outline of Final Research Achievements

During the last decade, increasing attention has been focused on the nucleolar stress pathway that releases ribosomal proteins from the nucleolus to the nucleoplasm when ribosome biosynthesis is abnormal and suppresses cell proliferation through p53 activation. On the other hand, it has been suggested that an abnormality in the ribosomal protein gene may promote canceration in studies of ribosomal protein mutants with Zebrafish model system and in epidemiological studies of ribosomopathy patients. In this study, we found that transcriptional inhibition of ribosomal RNA by an RNA polymerase inhibitor actinomycin D enhances the expression of down-stream target genes of the oncogenic transcriptional co-factors YAP1/TAZ and nuclear accumulation of YAP1 protein. Promoting effect of actinomycin D on the oncogenic growth signaling pathway may underlie the cancer promoting effect of ribosomal stress conditions and ribosomopathies.

Academic Significance and Societal Importance of the Research Achievements

本研究により、エネルギーの最大の消費過程であるリボソーム生合成過程と、近年がん治療の標的として大きな注目を浴びているHippo-YAP経路の関連が示唆された。これはリボソーム病の病態把握のみならず、リボソーム病に起因する悪性疾患の治療薬開発にもつながる可能性がある。また一般のがん細胞の多くでも、染色体異数性に伴うリボソーマル蛋白質遺伝子のコピー数変化や、発現異常がみられ、核小体ストレス作動状態にあると考えられる。そのため、本研究が、幅広いがんの病態把握や治療薬開発の一助になることも期待できる。

Report

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

    (3 results)

All 2020 2019 2018

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

  • [Journal Article] Enhanced processivity of Dnmt1 by monoubiquitinated histone H32020

    • Author(s)
      Y. Mishima, L. Brueckner, S. Takahashi, T. Kawakami, J. Otani, A. Shinohara, K. Takeshita, R. G. Garvilles, M. Watanabe, N. Sakai, H. Takeshima, C. Nachtegael, A. Nishiyama, M. Nakanishi, K. Arita, K. Nakashima, H. Hojo, I. Suetake
    • Journal Title

      Genes Cells

      Volume: 25 Issue: 1 Pages: 22-32

    • DOI

      10.1111/gtc.12732

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hippo pathway controls cell adhesion and context-dependent cell competition to influence skin engraftment efficiency2019

    • Author(s)
      Nishio Miki、Miyachi Yousuke、Otani Junji、Tane Shoji、Omori Hirofumi、Ueda Fumihito、Togashi Hideru、Sasaki Takehiko、Mak Tak Wah、Nakao Kazuwa、Fujita Yasuyuki、Nishina Hiroshi、Maehama Tomohiko、Suzuki Akira
    • Journal Title

      The FASEB Journal

      Volume: 33 Issue: 4 Pages: 5548-5560

    • DOI

      10.1096/fj.201802005r

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Hippoシグナル経路による細胞増殖変化と細胞間コミュニケーション2018

    • Author(s)
      西尾美希、宮地洋佑、大森裕文、上田史仁、大谷淳二、前濱朝彦、藤田恭之、仁 科博史、鈴木聡
    • Organizer
      第6回新学術領域「細胞競合」班会議 2018年6月14-15日 神戸
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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