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Studies on regulatory mechanism for cell migration based on chemical genetics

Research Project

Project/Area Number 19310146
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionKeio University

Principal Investigator

IMOTO Masaya  Keio University, 理工学部, 教授 (60213253)

Co-Investigator(Kenkyū-buntansha) TASHIRO Etsu  慶應義塾大学, 理工学部, 講師 (00365446)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2009: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2007: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Keywords遺伝子 / 癌 / シグナル伝達 / 5-リポキシゲナーゼ / ロイコトリエンC_4 / CysLT1 / 遊走 / ラメリポディア / Rac1 / UTKO-1 / 細胞遊走 / ビオチン標識 / Rac / フィロポディア / ピエリシジン
Research Abstract

UTKO1 was synthesized as a derivative of moverastin by Prof. Watanabe (Univ. Tokyo). We explored the mode of action of UTKO1 by using a chemical genetic approach. We found that UTKO1 inhibited EGF-induced cell migration by inhibiting Rac1 activation. To identify the molecular target of UTKO1, biotinylated UTKO1 was synthesized by Prof. Watanabe, and was used as the probe to obtain a target protein of UTKO1. As a result, 14-3-3ζ was identified as the functional target protein of UTKO1, because siRNA-mediated silencing of 14-3-3ζ expression suppressed both EGF-induced cell migration and Rac1 activation. These results suggest that 14-3-3ζ would act upstream of Rac1 activation in the process of EGF-induced cell migration, and UTKO1 inhibited cell migration possibly due to the abrogation of 14-3-3ζ function.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (33 results)

All 2010 2009 2008 2007 Other

All Journal Article (26 results) (of which Peer Reviewed: 26 results) Presentation (7 results)

  • [Journal Article] Mesenchyme cells can function to induce epithelial cell proliferation in starfish embryos.2010

    • Author(s)
      G. Hamanaka, M. Matsumoto, M. Imoto, H. Kaneko
    • Journal Title

      Develomental Dynamics 293

      Pages: 818-827

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchyme cells can function to induce epithelial cell proliferation in starfish embryos.2010

    • Author(s)
      G.Hamanaka, M.Matsumoto, M.Imoto, H.Kaneko
    • Journal Title

      Developmental Dynamics 293

      Pages: 818-827

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glyoxalase-I is a novel target against Bcr-Abl^+ leukemic cells acquiring stem-like characteristics in hypoxic environment.2010

    • Author(s)
      M.Takeuchi, S.Kimura, J.Kuroda, E.Ashihara, M.Kawatani, H.Osada, K.Umezawa, E.Yasui, M.Imoto, T.Tsuruo, A.Yokota, R.Tanaka, R.Nagao, T.Nakahata, Y.Fujiyama, T.Maekawa
    • Journal Title

      Cell Death Diff. (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oligomycin induced the proteasomal degradation of cyclin D1 protein.2009

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

      J. Antibiot 62

      Pages: 425-429

    • NAID

      10030635974

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] V-ATPase inhibitors overcome Bcl-xL-mediated chemoresistance through restoration of a caspase-independent apoptotic pathway.2009

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

      Cancer Science 100

      Pages: 1460-1467

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sakakibara. Integrating statistical predictions and experimental verifications for enhancing protein-chemical interaction predictions in virtual screening.2009

    • Author(s)
      N. Nagamine, T. Shirakawa, Y. Minato, K. Torii, H. Kobayashi, M. Imoto, Y. Sakakibara
    • Journal Title

      PLos Comput Biol e1000397

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of human fibroblast growth factor receptor 1 by E2F-1.2009

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

      Gene 438

      Pages: 49-53

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oligomycin induced the proteasomal degradation of cyclin D1 protein2009

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

      J.Antibiot 62

      Pages: 425-429

    • NAID

      10030635974

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase2008

    • Author(s)
      M. Kawatani, H. Okumura, K Honda, N. Kanoh, M. Muroi, N. Dohmae, M. Takami, M. Kitagawa, Y. Futamura, M. Imoto, H. Osada
    • Journal Title

      I. Proc. Natl. Acad. Sci. U S A 105

      Pages: 11691-11696

    • Related Report
      2009 Final Research Report
    • 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, Biological Activities and SAR Study.2008

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

      J. Antibiot 61

      Pages: 303-311

    • NAID

      10021927806

    • Related Report
      2009 Final Research Report
    • 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 Elucidation.2008

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

      J. Antibiot 61

      Pages: 312-317

    • NAID

      10021927823

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bcl-xL from Microbial Origin.2008

    • 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

      J. Am. Chem. Soc. 130

      Pages: 1822-1823

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of mouse type II platelet-derived growth factor receptor a transcript.2008

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

      Biosci. Biotechnol. Biochem. 72

      Pages: 759-766

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and antitumor activity of combretastatin D-4.2008

    • Author(s)
      K. Uno, T. Tanabe, T. Ogamino, R. Okada, M. Imoto, S. Nishiyama
    • Journal Title

      Heterocycles 75

      Pages: 291-296

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bel-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

      J. Am. Chem. Soc. 130

      Pages: 1822-1823

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of mouse type II platelet-derived growth factor receptor α transcript.2008

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

      Biosci. Biotechnol. Biochem. 72

      Pages: 759-766

    • NAID

      10027525635

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I2008

    • Author(s)
      M. Kawatani, H. Okumura, K Honda, N. Kanoh, M. Muroi, N. Dohmae, M. Takami, M. Kitagawa, Y. Futamura, M. Imoto, H. Osada
    • Journal Title

      Proc. Natl. Acad. Sci. USA 105

      Pages: 11691-11696

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bcl-xL from Microbial Origin.2008

    • Author(s)
      Y. Futamura, et. al., and M. Imoto
    • Journal Title

      J.Am.Chem.Soc 130

      Pages: 1822-1823

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of mouse type II platelet-derived growth factor receptor a transcript.2008

    • Author(s)
      Y. Minato, et. al. and M. Imoto
    • Journal Title

      Biosci.Biotechnol.Biochem., 72

      Pages: 759-766

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trierixin, a Novel Inhibitor of ER stress-induced XBP1 Activation from Streptomyces sp. I. Taxonomy, Fermentation, Isolation, and Biological activities.2007

    • Author(s)
      E. Tashiro, N. Hironiwa, M. Kitagawa, Y. Futamura, M. Imoto
    • Journal Title

      J. Antiobiot 60

      Pages: 547-553

    • NAID

      10019830891

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Trierixin, a Novel Inhibitor of ER Stress-induced XBP1 Activation from Streptomyces sp. II. Structure Elucidation2007

    • Author(s)
      Y. Futamura, E. Tashiro, N. Hironiwa, J. Kohno, M. Nishio, K. Shindo, M. Imoto
    • Journal Title

      J. Antiobiot 60

      Pages: 582-585

    • NAID

      10019831014

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of a new variant of human platelet-derived growth factor receptor a transcript by E2F-1.2007

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

      Gene 403

      Pages: 89-97

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functions of cyclin D1 as an oncogene and regulation of cyclin D1 expression.2007

    • Author(s)
      E. Tashiro, A. Tsuchiya, M. Imoto
    • Journal Title

      Cancer Science 98

      Pages: 629-635

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of PP2A nuclear accumulation and subsequent inactivation of AP-1 in leptomycin B-inhibited cyclin D1 expression.2007

    • Author(s)
      A. Tsuchiya, E. Tashiro, M. Yoshida, M. Imoto
    • Journal Title

      Oncogene 26

      Pages: 1522-1532

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Trierixin,a Novel Inhibitor of ER stress-induced XBP1 Activation from Streptomyces sp.I.Taxonomy,Fermentation,Isolation,and Biological activides.2007

    • Author(s)
      E. Tashiro, et. al. and M. Imoto:
    • Journal Title

      J.Antiobiot 60

      Pages: 547-553

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in hypoxic environment.

    • Author(s)
      M. Takeuchi, S. Kimura, J. Kuroda, E. Ashihara, M. Kawatani, H. Osada, K. Umezawa, E. Yasui, M. Imoto, T. Tsuruo, A. Yokota, R. Tanaka, R. Nagao, T. Nakahata, Y. Fujiyama, T. Maekawa
    • Journal Title

      Cell Death Diff. (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Presentation] Studies on the mechanism for inhibition of tumor cell migration by UTKO12009

    • Author(s)
      高野圭
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Studies on the Regulatory Mechanism for Cell Migration Based on Chemical Gonomics2009

    • Author(s)
      間木重行
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Studies on the mechanism for inhibition of tumor cell migration by UTKO12009

    • Author(s)
      小林大貴
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] ケミカルバイオロジーによる細胞遊走シグナル伝達機構の解析2009

    • Author(s)
      間木重行
    • Organizer
      日本ケミカルバイオロジー学会第4回年会
    • Place of Presentation
      神戸
    • Year and Date
      2009-05-19
    • Related Report
      2009 Final Research Report
  • [Presentation] ケミカルシステムバイオロジーによる細胞遊走シグナル伝達機構の解析2009

    • Author(s)
      間木重行
    • Organizer
      日本ケミカルバイオロジー学会第4回年会
    • Place of Presentation
      神戸
    • Year and Date
      2009-05-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] メタボローム解析を用いたケミカルバイオロジー2008

    • Author(s)
      井本正哉
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Inhibition of tumor cell migration by BU-4664L2007

    • Author(s)
      Yasushi Takemoto, Etsu Tashiro and Masaya Imoto
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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