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Elucidation of the role of PERK signaling pathway in tumor microenvironment and its application for drug discovery

Research Project

Project/Area Number 24650626
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

TOMIDA Akihiro  公益財団法人がん研究会, がん化学療法センター, ゲノム研究部 部長 (40251483)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsがん微小環境 / UPR / 小胞体ストレス / PERK / グルコース飢餓 / 低酸素 / がん
Outline of Final Research Achievements

The UPR (unfolded protein response) is a cellular adaptive mechanism that plays an important role in cancer cell survival and proliferation within particular tumor microenvironment. In this study, we focused on two proteins: one is PERK, a central regulatory protein in the UPR, and the other is TBL2, a new function molecule which can interact with PERK during stress. Then, we examined roles of the PERK signaling pathway in cancer cell adaptation to tumor microenvironment by knocking down PERK or TBL2. In addition, aiming at the development of treatment strategy, we searched factors which had a synthetic lethal relationship under conditions inhibiting function of the PERK signaling pathway.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (20 results)

All 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (10 results) (of which Invited: 1 results) Remarks (3 results)

  • [Journal Article] TBL2 is a novelPERK-binding protein that modulates stress-signaling and cell survival during endoplasmic reticulum stress.2014

    • Author(s)
      Tsukumo Y, Tsukahara S, Furuno A, Iemura S, Natsume T, Tomida A
    • Journal Title

      PLOS ONE

      Volume: 13:9(11) Issue: 11 Pages: e112761-e112761

    • DOI

      10.1371/journal.pone.0112761

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of ATP citrate lyase induces triglyceride accumulation with altered fatty acid composition in cancer cells.2014

    • Author(s)
      5.Migita T, Okabe S, Ikeda K, Igarashi S, Sugawara S, Tomida A, Soga T, Taguchi R, Seimiya H.
    • Journal Title

      Int J Cancer.

      Volume: 135 Issue: 1 Pages: 37-47

    • DOI

      10.1002/ijc.28652

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ultrastructural localization of intravenously injected carbon nanohorns in tumor.2014

    • Author(s)
      Matsumura S, Yuge R, Sato S, Tomida A, Ichihashi T, Irie H, Iijima S, Shiba K, Yudasaka M.
    • Journal Title

      Int J Nanomedicine

      Volume: 9 Pages: 3499-3508

    • DOI

      10.2147/ijn.s62688

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a gene expression database and related analysis programs for evaluation of anticancer compounds.2013

    • Author(s)
      Ushijima M, Mashima T, Tomida A, Dan S, Saito S, Furuno A, Tsukahara S, Seimiya H, Yamori T, Matsuura M.
    • Journal Title

      Cancer Sci.

      Volume: 104(3) Issue: 3 Pages: 360-368

    • DOI

      10.1111/cas.12071

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of ATP citrate lyase induces an anticancer effect via reactive oxygen species: AMPK as a predictive biomarker for therapeutic impact2013

    • Author(s)
      Migita, T., Okabe, S., Ikeda, K., Igarashi, S., Sugawara, S., Tomida, A., Taguchi, R., Soga, T., Seimiya, H.
    • Journal Title

      Am J Pathol.

      Volume: 182 Issue: 5 Pages: 1800-1810

    • DOI

      10.1016/j.ajpath.2013.01.048

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling2012

    • Author(s)
      Saito S, Furuno A, Sakurai J, Park HR, Shin-ya K, Tomida A
    • Journal Title

      PLoS One

      Volume: 7 Issue: 9 Pages: e45845-e45845

    • DOI

      10.1371/journal.pone.0045845

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-in duced cyto toxicity during glucose deprivation2012

    • Author(s)
      Matsuo J, Tsukumo Y, Saito S, Tsukahara S, Sakurai J, Sato S, Kondo H, Ushijima M, Matsuura M, Watanabe T, Tomida A
    • Journal Title

      Mol Cancer Ther

      Volume: 11(5) Issue: 5 Pages: 1082-1091

    • DOI

      10.1158/1535-7163.mct-11-0871

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] UPR標的遺伝子の発現変化を伴って細胞毒性を示すmiRNA阻害剤の同定2014

    • Author(s)
      岡本有加,小井土大,塚原里美,国政和宏,冨田章弘.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] オートファジー阻害剤spautin-1のグルコース飢餓選択的な殺細胞作用2014

    • Author(s)
      国政和宏,冨田章弘.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 嫌気的環境下においてミトコンドリアを介して活性化するHIF-1の新たな転写活性制御機構2014

    • Author(s)
      小井土大,芳賀直実,塚原里美,佐藤重男,冨田章弘.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] がん細胞増殖抑制効果を有するヒトmicroRNA阻害剤の探索2014

    • Author(s)
      岡本有加,国政和宏,冨田章弘.
    • Organizer
      第18回日本がん分子標的治療学会学術集会
    • Place of Presentation
      仙台市情報・産業プラザ(宮城県仙台市)
    • Year and Date
      2014-06-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] オートファジー阻害剤spautin-1はグルコース飢餓誘導性の小胞体ストレス応答を抑制する2014

    • Author(s)
      国政和宏,冨田章弘.
    • Organizer
      第18回日本がん分子標的治療学会学術集会
    • Place of Presentation
      仙台市情報・産業プラザ(宮城県仙台市)
    • Year and Date
      2014-06-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 細胞内ストレス:がん細胞の特徴的代謝とストレス応答

    • Author(s)
      冨田章弘
    • Organizer
      日本がん分子標的治療学会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] がん微小環境標的治療の分子標的としての新規ストレス応答UPR制御因子TBL2

    • Author(s)
      冨田章弘,築茂由則,塚原里美
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] がん微小環境ストレスに適応したミトコンドリアDNA欠損がん細胞株の樹立とその性状解析

    • Author(s)
      冨田章弘
    • Organizer
      第16回日本がん分子標的治療学会学術集会
    • Place of Presentation
      北九州
    • Related Report
      2012 Research-status Report
  • [Presentation] がん微小環境標的治療法の開発を目指したがん細胞のグルコース飢餓への新たな適応機構の解析

    • Author(s)
      冨田章弘
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] がん微小環境ストレスに適応したミトコンドリアDNA欠損がん細胞の樹立とその発現解析

    • Author(s)
      冨田章弘
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Remarks] がん研究会がん化学療法センターゲノム研究部ホームページ

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/genome/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 公益財団法人がん研究会がん化学療法センターゲノム研究部

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/genome/index.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 公益財団法人がん研究会がん化学療法センターゲノム研究部

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/genome/index.html

    • Related Report
      2012 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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