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Roles of importin alpha1 in tumor microenvironment

Research Project

Project/Area Number 16K18434
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionJikei University School of Medicine

Principal Investigator

Yamada Kohji  東京慈恵会医科大学, 医学部, 助教 (90570979)

Research Collaborator Yoneda Yoshihiro  
Oka Masahiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords核輸送因子 / 肝がん / 細胞外局在 / 肝癌 / がん / 微小環境 / 細胞外放出 / 癌 / 生体分子 / 蛋白質 / 病理学
Outline of Final Research Achievements

Liver cancers are among the common cancers and the fifth leading cause of cancer mortality in Japan. Surgical resection and liver transplantation are the only curative treatments for early-stage patients with liver cancers. However, the majority of patients are diagnosed in advanced stages of the disease during which the extant therapies are ineffective. Therefore, it is important for developing novel therapy to target for liver cancers.
This study showed that intracellular nuclear trafficking protein, importin alpha 1, was localized at the extracellular space. Extracellular importin alpha 1 was specifically detected in liver cancer cell lines. In mouse subcutaneous model, extracellular importin alpha 1 was localized at the cell surface of mouse-derived vascular endothelial cells, as well as human cancer cells. These data suggested that extracellular importin alpha 1 was involved in tumor microenvironment.

Academic Significance and Societal Importance of the Research Achievements

肝癌は現在も依然として患者数が多く、年間約3万人が死亡しており、その疾患対策が求められている。肝癌は再発を繰り返しやすく、他の悪性腫瘍と比較して長期生存の困難な疾患でもあり、背景肝疾患からの肝癌を早期に判別できるバイオマーカーや肝癌を根治する療法の開発は治療成績に大きく影響することから臨床的ニーズは極めて高い。本研究によって、肝癌特異性の高い新しい機構として核移行タンパク質の細胞外局在を先駆的に提示することができた。今後、診断や治療への応用が見込まれる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2019 2018 2017 2016 Other

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Mechanical insights into the regulation of programmed cell death by p53 via mitochondria.2019

    • Author(s)
      Kohji Yamada, Kiyotsugu Yoshida
    • Journal Title

      Biochim Biophys Acta Mol Cell Res

      Volume: 1866 Issue: 5 Pages: 839-848

    • DOI

      10.1016/j.bbamcr.2019.02.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Importin α: a key molecule in nuclear transport and non-transport functions.2016

    • Author(s)
      Miyamoto Y, Yamada K, Yoneda Y.
    • Journal Title

      J Biochem

      Volume: 160 Issue: 2 Pages: 69-75

    • DOI

      10.1093/jb/mvw036

    • NAID

      40020914020

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Two isoforms of TALDO1 generated by alternative translational initiation show differential nucleocytoplasmic distribution to regulate the global metabolic network.2016

    • Author(s)
      Moriyama T, Tanaka S, Nakayama Y, Fukumoto M, Tsujimura K, Yamada K, Bamba T, Yoneda Y, Fukusaki E, Oka M.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 34648-34648

    • DOI

      10.1038/srep34648

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Extracellular released importin α1 stimulates proliferation of cancer cells2016

    • Author(s)
      山田幸司、米田悦啓、岡正啓
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-12-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of cell surface localization of a nuclear transport factor importin α1 and its significance in FGF signaling2016

    • Author(s)
      K. Yamada, Y. Yoneda
    • Organizer
      The 41st Naito Conference
    • Place of Presentation
      北海道
    • Year and Date
      2016-07-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Cold stimulation evokes cellular sensitivity to antinuclear antibodies of patients with systemic sclerosis via induction of cell surface localization of hnRNP-K2016

    • Author(s)
      山田幸司、世良田聡、岡正啓、藤本穣、仲哲治、米田悦啓
    • Organizer
      第68回日本分子生物学会年会・第11回日本ケミカルバイオロジー学会 合同学会
    • Place of Presentation
      京都
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
  • [Book] 人体の細胞生物学2018

    • Author(s)
      山田 幸司、米田 悦啓
    • Total Pages
      20
    • Publisher
      日本医事新報社
    • ISBN
      9784784932320
    • Related Report
      2018 Annual Research Report
  • [Book] 次世代がん治療2017

    • Author(s)
      山田幸司、米田悦啓、岡正啓
    • Total Pages
      347
    • Publisher
      NTS
    • ISBN
      9784860435035
    • Related Report
      2017 Research-status Report
  • [Remarks] 核輸送因子インポーティンα1の新たな機能の発見

    • URL

      http://www.nibiohn.go.jp/information/nibio/2016/03/004613.html

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 新規肝癌マーカー2018

    • Inventor(s)
      山田幸司、吉田清嗣
    • Industrial Property Rights Holder
      東京慈恵会医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-095674
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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