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2010 Fiscal Year Final Research Report

Studies on the role of XBP1 in tumor malignancy

Research Project

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Project/Area Number 20611016
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical biology
Research InstitutionKeio University

Principal Investigator

TASHIRO Etsu  Keio University, 理工学部, 講師 (00365446)

Co-Investigator(Kenkyū-buntansha) IMOTO Masaya  慶應義塾大学, 理工学部, 教授 (60213253)
Project Period (FY) 2008 – 2010
Keywords小胞体ストレス / XBP1 / 固形がん悪性化
Research Abstract

Poorly vascularized solid-tumor cells encounter a range of cytotoxic conditions such as hypoxia and nutrient deprivation, which cause ER stress. These cytotoxic conditions in solid tumors are considered to adapt to ER stress by activating X-box binding protein 1 (XBP1). Therefore, we have been screening for an inhibitor of XBP1 activation, and we succeeded to identify three small molecule inhibitors. As we investigated the molecular mechanism by which these small molecule inhibitors inhibited XBP1, we found that toyocamycin strongly inhibited XBP1 and induced apoptosis in cancer cells only under ER stressed condition. Therefore, toyocamycin would be an inhibitor as a new molecular target therapy of cancer.

  • Research Products

    (24 results)

All 2011 2010 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (11 results) Remarks (1 results)

  • [Journal Article] Quinotrierixin inhibited ER stress-induced XBP1 mRNA splicing through inhibition of protein synthesis2011

    • Author(s)
      K.Yamamoto, E.Tashiro, M.Imoto
    • Journal Title

      Biosci Biotechnol Biochem 75

      Pages: 284-288

    • Peer Reviewed
  • [Journal Article] A new, convenient cell-based screening method for small-molecule glycolytic inhibitors2011

    • Author(s)
      M.Kitagawa, M.Misawa, S.Ogawa, E.Tashiro, M.Imoto
    • Journal Title

      Biosci Biotechnol Biochem 75

      Pages: 367-369

    • Peer Reviewed
  • [Journal Article] Synthesis and anti-migrative evaluation of moverastin derivatives2011

    • Author(s)
      M.Sawada, S.Kubo, K.Matsumura, Y.Takemoto, H.Kobayashi, E.Tashiro, T.Kitahara, H.Watanabe, M.Imoto
    • Journal Title

      Bioorg Med Chem Lett 21

      Pages: 1385-1389

    • Peer Reviewed
  • [Journal Article] Metabolomic identification of the target of the filopodia protrusion inhibitor glucopiericidin A2010

    • Author(s)
      M.Kitagawa, S.Ikeda, E.Tashiro, T.Soga, M.Imoto
    • Journal Title

      Chemistry and Biology 17

      Pages: 989-998

    • Peer Reviewed
  • [Journal Article] Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp.MK756-CF12010

    • Author(s)
      T.Kawamura, T.Fujimaki, N.Hamanaka, K.Torii, H.Kobayashi, Y.Takahashi, M.Igarashi, N.Kinoshita, Y.Nishimura, E.Tashiro, M.Imoto
    • Journal Title

      J.Antibiot(Tokyo) 63

      Pages: 601-605

    • Peer Reviewed
  • [Journal Article] Oligomycin induced the proteasomal degradation of cyclin D12009

    • Author(s)
      M.Kanai, S.Iba, R.Okada, E.Tashiro, M.Imoto
    • Journal Title

      J.Antibot(Tokyo) 62

      Pages: 425-429

    • Peer Reviewed
  • [Journal Article] V-ATPase Inhibitors Overcome Bcl-xL-mediated Chemoresistance through Restoration of a Caspase-independent Apoptotic Pathway2009

    • Author(s)
      Y.Sasazawa, Y.Futamura, E.Tashiro, M.Imoto
    • Journal Title

      Cancr Science 100

      Pages: 1460-1467

    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of human fibroblast growth factor receptor 1 by E2F-12009

    • Author(s)
      M.Kanai, E.Tashiro, H.Maruki, Y.Minato, M.Imoto
    • Journal Title

      Gene 438

      Pages: 49-56

    • Peer Reviewed
  • [Journal Article] SAR study of a Novel Triene-ansamycin Group Compound, Quinotrierixin, and Related Compounds, as Inhibitors of ER Stress-induced XBP1 Activation. I.Taxonomy, Fermentation, Isolation, and Biological activities and SAR study2008

    • Author(s)
      T.Kawamura, E.Tashiro, K.Yamamoto, K Shindo, M.Imoto
    • Journal Title

      J.Antibiot(Tokyo) 61

      Pages: 303-311

    • Peer Reviewed
  • [Journal Article] SAR study of a Novel Triene-ansamycin Group Compound, Quinotrierixin, and Related Compounds, as Inhibitors of ER Stress-induced XBP1 Activation. II.Structure Elucidation2008

    • Author(s)
      T.Kawamura, E.Tashiro, K.Shindo, M.Imoto
    • Journal Title

      J.Antibiot(Tokyo) 61

      Pages: 312-317

    • Peer Reviewed
  • [Journal Article] Identification and characterization of mouse type II platelet-derived growth factor receptor a transcript2008

    • Author(s)
      Y.Minato, Y.Nihei, Y.Kodama, E.Tashiro, M.Kanai, M.Imoto
    • Journal Title

      Biosci.Biotechnol.Biochem. 72

      Pages: 759-766

    • Peer Reviewed
  • [Journal Article] Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bcl-xL from Microbial Origin2008

    • Author(s)
      Y.Futamura, R.Sawa, Y.Umezawa, M.Igarashi, H.Nakamura, K.Hasegawa, M.Yamasaki, E.Tashiro, Y.Takahashi, Y.Akamatsu, M.Imoto
    • Journal Title

      The Journal of American Chemical Society 130

      Pages: 1822-1823

    • Peer Reviewed
  • [Presentation] Identification of Trierixin as a novel inhibitor for ER stress-oinduced XBP1 activation from Streptomyces sp.2010

    • Author(s)
      田代悦, 井本正哉
    • Organizer
      アジアコアプログラム第2回合同セミナー
    • Place of Presentation
      タイ・コンケン
    • Year and Date
      2010-11-21
  • [Presentation] 放線菌由来新規テルペン化合物NT17Aによる細胞死誘導機構の解析2010

    • Author(s)
      小田一成、田代悦、本橋慶一郎、瀬戸治男、井本正哉
    • Organizer
      日本農芸化学会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-29
  • [Presentation] Toyocamycin inhibits ER stress-induced XBP1 mRNA splicing through IRE1a inhibition2009

    • Author(s)
      Etsu Tashiro, Yumi Yokouchi, 山本浩太, 井本正哉
    • Organizer
      AACR-NCI-EORTC合同国際カンファレンス
    • Place of Presentation
      ボストン
    • Year and Date
      2009-11-16
  • [Presentation] 新規XBP1阻害剤キノトリエリキシンは不良タンパク質の蓄積を阻害することで小胞体ストレスを抑制する2009

    • Author(s)
      山本浩太、田代悦、井本正哉
    • Organizer
      ケミカルバイオロジー学会
    • Place of Presentation
      神戸
    • Year and Date
      2009-05-18
  • [Presentation] BrefeldinAが誘導する小胞体ストレス応答の制御機構解析2009

    • Author(s)
      新荘聡子、田代悦、井本正哉
    • Organizer
      日本農芸化学会
    • Place of Presentation
      福岡
    • Year and Date
      2009-03-27
  • [Presentation] 新規XBP1活性化阻害剤トリエリキシンの発見2008

    • Author(s)
      田代悦、二村友史、井本正哉
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2008-10-28
  • [Presentation] 小胞体ストレスが誘導する転写因子XBP1の活性化を抑制する新規化合物トリエリキシンとキノトリエリキシンの発見・構造解析・生物活性・構造活性相関2008

    • Author(s)
      河村達郎、田代悦、二村友史、新藤一敏、井本正哉
    • Organizer
      天然有機化合物討論会
    • Place of Presentation
      福岡
    • Year and Date
      2008-09-30
  • [Presentation] トリエリキシンおよびその類縁体のXBP1阻害活性および抗腫瘍活性の評価2008

    • Author(s)
      河村達郎、田代悦、井本正哉
    • Organizer
      がん分子標的治療研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-26
  • [Presentation] トヨカマイシンによるXBP1 活性化阻害機構の解析2008

    • Author(s)
      田代悦、井本正哉
    • Organizer
      がん分子標的治療研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-26
  • [Presentation] 小分子化合物と統計処理を用いた小胞体ストレス応答機構の解析2008

    • Author(s)
      新庄聡子、田代悦、井本正哉
    • Organizer
      日本ケミカルバイオロジー研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-19
  • [Presentation] トヨカマイシンによるXBP1活性化阻害機構の解析2008

    • Author(s)
      田代悦、井本正哉
    • Organizer
      日本ケミカルバイオロジー研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-19
  • [Remarks] ホームページ等

    • URL

      http://www.bio.keio.ac.jp/labs/imoto/

URL: 

Published: 2012-01-26   Modified: 2016-04-21  

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