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Analysis of mechanism of serine protease activation by membrane-type matrix metalloproteinase

Research Project

Project/Area Number 25460382
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionKanazawa University

Principal Investigator

Sato Hiroshi  金沢大学, がん進展制御研究所, 教授 (00115239)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsがん転移 / マトリックスメタロプロテアーゼ / MT1-MMP / HAI-1 / セリンプロテアーゼ / MMP-9 / マトリプターゼ
Outline of Final Research Achievements

Membrane-Type Matrix Metalloproteinase (MT1-MMP) was shown to cleave and inactivate membrane-type serine protease inhibitor HAI-1(Hepatocyte Growth Factor Inhibitor-1), which subsequently induced activation of matriptase. Activated matriptase induced further activation of serine protease cascade, which was named “Protease Storm”. Protease storm caused Epithelial-Mesenchymal Transition (EMT) in cancer cells. These results indicate that MT1-MMP contributes to malignant transformation of cancer cells by triggering protease activation cascade.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (24 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway2016

    • Author(s)
      Takino T, Nakada M, Li Z, Yoshimoto T, Domoto T, Sato H.
    • Journal Title

      Clinical & Experimental Metastasis

      Volume: 33 Issue: 1 Pages: 45-52

    • DOI

      10.1007/s10585-015-9756-8

    • NAID

      120005680038

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] NECAB3 Promotes Activation of Hypoxia-inducible factor-1 during Normoxia and Enhances Tumourigenicity of Cancer Cells2016

    • Author(s)
      1.Nakaoka HJ, Hara T, Yoshino S, Kanamori A, Matsui Y, Shimamura T, Sato H, Murakami Y, Seiki M, Sakamoto T
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 22784-22784

    • DOI

      10.1038/srep22784

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Suppressing TGFβ signaling in regenerating epithelia in an inflammatory microenvironment is sufficient to cause invasive intestinal cancer.2015

    • Author(s)
      Oshima H, Nakayama M, Han TS, Naoi K, Ju X, Maeda Y, Robine S, Tsuchiya K, Sato T, Sato H, Taketo MM, Oshima M.
    • Journal Title

      Cancer Res.

      Volume: 75 Issue: 4 Pages: 766-776

    • DOI

      10.1158/0008-5472.can-14-2036

    • NAID

      120005593962

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1 and c-Jun N-terminal kinase-mediated pathway.2015

    • Author(s)
      Chikano Y, Domoto T, Furuta T, Sabit H, Kitano-Tamura A, Ilya V. Pyko, Takino T, Sai Y, Hayashi Y, Sato H, Miyamoto K, Nakada M, MinamotoT.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 14 Issue: 2 Pages: 564-574

    • DOI

      10.1158/1535-7163.mct-14-0479

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly and N-cadherin adhesion.2014

    • Author(s)
      Takino T, Yoshimoto T, Nakada M, Li Z, Domoto T, Kawashiri S, Sato H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 450 Issue: 2 Pages: 1016-1020

    • DOI

      10.1016/j.bbrc.2014.06.100

    • NAID

      120005478703

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway.2014

    • Author(s)
      Yoshimoto T, Takino T, Li Z, Domoto T, Sato H
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 455 Issue: 3-4 Pages: 251-255

    • DOI

      10.1016/j.bbrc.2014.10.154

    • NAID

      120005537877

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterizing invading glioma cells based on IDH1-R132H and Ki-67 immunofluorescence.2014

    • Author(s)
      Sabit H, Nakada M, Furuta T, Watanabe T, Hayashi Y, Sato H, Kato Y, Hamada JI.
    • Journal Title

      Brain Tumor Pathol

      Volume: 未定 Issue: 4 Pages: 3-3

    • DOI

      10.1007/s10014-013-0172-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] MT1-MMP prevents growth inhibition by three dimensional fibronectin matrix.2013

    • Author(s)
      1. Takino T, Guo L, Domoto T, Sato H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 30 Pages: 175-179

    • NAID

      120005302290

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 炎症反応とTGFbシグナル抑制による大腸がん浸潤誘導2015

    • Author(s)
      大島浩子、中山瑞穂、佐藤博、武藤誠、大島正伸
    • Organizer
      日本癌学会
    • Place of Presentation
      愛知県名古屋市 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] GSK3bはFAK/JNK経路を介するMMPsの発現亢進によって膠芽腫細胞の浸潤を推進する2015

    • Author(s)
      堂本貴寛、古田拓也、滝野隆久、佐藤博、中田光俊、源利成
    • Organizer
      日本癌学会
    • Place of Presentation
      愛知県名古屋市 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] VinculinはMEK/ERK経路を介したMT1-MMPの転写を不に制御する2015

    • Author(s)
      吉本泰祐、滝野隆久、堂本貴寛、川尻秀一、佐藤博
    • Organizer
      日本癌学会
    • Place of Presentation
      愛知県名古屋市 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tip60はNF-kB経路を介して膠芽腫のMT1-MMP発現と浸潤を制御する2015

    • Author(s)
      滝野隆久、中田光俊、堂本貴寛、佐藤博
    • Organizer
      日本癌学会
    • Place of Presentation
      愛知県名古屋市 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] VinculinはMEK/ERK経路を介したMT1-MMPの転写を不に制御する2015

    • Author(s)
      吉本泰祐、滝野隆久、堂本貴寛、川尻秀一、佐藤博
    • Organizer
      日本がん転移学会
    • Place of Presentation
      大阪府大阪市 シティプラザ大阪
    • Year and Date
      2015-07-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] GSK3bはFAK-Rac1-JNK経路を介して膠芽腫細胞の浸潤を推進する2015

    • Author(s)
      堂本貴寛、滝野隆久、佐藤博、源利成
    • Organizer
      日本がん転移学会
    • Place of Presentation
      大阪府大阪市 シティプラザ大阪
    • Year and Date
      2015-07-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] MT1-MMPによる細胞接着斑を介したフィブロネクチンマトリックス形成制御2014

    • Author(s)
      滝野隆久、吉本泰祐、佐藤博
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] TX-2137をリード化合物としたAkt選択的抗転移低酸素サイトトキシンTX-2282の開発2014

    • Author(s)
      芝一休、遠藤良夫、佐藤博、宇都義浩
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 慢性炎症とTGFbシグナル抑制による消化管腫瘍の浸潤誘導2014

    • Author(s)
      大島浩子、中山瑞穂、佐藤博、武藤誠、大島正伸
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] MT1-MMPによるフィブロネクチン重合とN-カドヘリン接着の制御2014

    • Author(s)
      吉本泰祐、滝野隆久、川尻修一、佐藤博
    • Organizer
      第23回日本がん転移学会学術総会
    • Place of Presentation
      金沢(金沢市文化ホール)
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Presentation] MT1-MMPによる細胞接着ネットワークの制御2013

    • Author(s)
      滝野 隆久,堂本 貴寛,佐藤 博
    • Organizer
      第21回日本がん転移学会総会
    • Place of Presentation
      松本
    • Related Report
      2013 Research-status Report
  • [Presentation] MT1-MMPによるN-カドヘリン接着制御2013

    • Author(s)
      滝野 隆久,堂本 貴寛,佐藤 博
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Book] 実験医学2015

    • Author(s)
      佐藤 博
    • Total Pages
      4
    • Publisher
      羊土社
    • Related Report
      2015 Annual Research Report
  • [Book] がん微小環境と標的治療2015

    • Author(s)
      滝野隆久、 佐藤博
    • Total Pages
      207
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report
  • [Remarks] 金沢大学がん進展制御研究所

    • URL

      http://www.kanazawa-u.ac.jp/~ganken/

    • Related Report
      2014 Research-status Report
  • [Remarks] 金沢大学がん進展制御研究所

    • URL

      http://www.kanazawa-u.ac.jp/~ganken/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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