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Radiosensitization by mitochondrial ROS amplification

Research Project

Project/Area Number 15H05674
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionHokkaido University

Principal Investigator

Onodera Yasuhito  北海道大学, 医学研究院, 講師 (90435561)

Research Collaborator NAM Jin-Min  北海道大学, 国際連携研究教育局(GI-CoRE), 講師 (60414132)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsミトコンドリア / 活性酸素 / 放射線 / 小胞輸送 / インテグリン / 活性酸素種 / がん
Outline of Final Research Achievements

Arf6 and AMAP1 are highly expressed in different cancers including breast cancer, and mediate integrin recycling to plasma membrane to promote cancer invasion and metastasis. On the other hand, signaling downstream of integrins is well known to contribute to resistance to radiation and chemotherapy. In this study, we have shown that reduction of the integrin signaling by blockade of the Arf6-AMAP1 pathway inhibits intracellular mitochondrial distribution, resulting in aggregated mitochondria around the nucleus, which induces amplification of the reactive oxygen species (ROS) produced by ionizing radiation. We have also revealed molecules involved in the regulation of mitochondrial distribution downstream of integrins, and how they interact with each other. Further analyses may lead to the establishment of a new modality for radio-sensitization, which is based on the ROS amplification mediated by mitochondrial aggregation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (8 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (7 results) (of which Invited: 6 results)

  • [Journal Article] Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells.2017

    • Author(s)
      Wu PH, Onodera Y, Ichikawa Y, Rankin EB, Giaccia AJ, Watanabe Y, Qian W, Hashimoto T, Shirato H, Nam JM.
    • Journal Title

      Int J Nanomedicine.

      Volume: 14 Pages: 5069-5085

    • DOI

      10.2147/ijn.s137833

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Integrin Signaling and Cancer Metabolism2017

    • Author(s)
      小野寺康仁、佐邊壽孝
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリア分布の調節による酸化ストレスの制御2016

    • Author(s)
      小野寺康仁
    • Organizer
      臨床フリーラジカル会議
    • Place of Presentation
      京都・烟河(京都府亀岡市)
    • Year and Date
      2016-01-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 代謝と輸送および区画化を介したがん形質の誘導2016

    • Author(s)
      小野寺康仁、Mina Bissell、佐邊壽孝
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ(京都市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] がん形質の獲得と代謝の局所制御2016

    • Author(s)
      小野寺康仁、堀川芽衣、佐邊壽孝
    • Organizer
      第4回がんと代謝研究会
    • Place of Presentation
      かごしま県民交流センター(鹿児島市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] がん細胞における小胞輸送経路を介した ミトコンドリア分布制御と 活性酸素および放射線への耐性2016

    • Author(s)
      小野寺康仁、南ジンミン、白土 博樹、佐邊壽孝
    • Organizer
      第59回放射線影響学会
    • Place of Presentation
      JMSアステールプラザ(広島市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Arf6-AMAP1 pathway confers radioresistance via regulation of ROS in breast cancer2015

    • Author(s)
      小野寺康仁
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 糖代謝と小胞輸送の相互作用を介したがん形質の誘導2015

    • Author(s)
      小野寺康仁
    • Organizer
      がんと代謝研究会
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Year and Date
      2015-07-16
    • Related Report
      2015 Annual Research Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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