Study on role of membrane-type matrix metalloproteinase-1 in tumor malignancy

• Project/Area Number: 21390091
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kanazawa University
• Principal Investigator: SATO Hiroshi 金沢大学, がん進展制御研究所, 教授 (00115239)
• Co-Investigator(Kenkyū-buntansha): TAKINO Takahisa 金沢大学, がん進展制御研究所, 准教授 (40322119) ; NAKADA Mitsutoshi 金沢大学, 医学系, 講師 (20334774)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2009: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: MT1-MMP / がん転移 / 浸潤 / 細胞外マトリックス / プロテアーゼ / シェディング / HAI-1 / KIM-1 / 転移 / 悪性化 / 運動 / MMP-2 / 幹細胞

Research Abstract

We screened new substrates for MT1-MMP, which plays an important role in tumor invasion and metastasis, and analyzed pathophysiologicanl significance of it. These studies demonstrated that cleavage and shedding of membrane proteins by MT1-MMP is quite unique. For example, cleavage of serine protease inhibitor Hepatocyte Growth Factor Activator Inhibitor-1 by MT1-MMP initiates protease activation cascade, which subsequently causes tissue destruction. We named it as protease storm.

Research Products

• [Journal Article] Cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase (2012)
  • Author(s): Domoto T, Takino T, Guo L, Sato, H.
  • Journal Title: Cancer Sci. Volume: 103 Issue: 3 Pages: 448-454
  • DOI: 10.1111/j.1349-7006.2011.02162.x
  • NAID: 120005767273
  • Peer Reviewed
• [Journal Article] Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly to promote cell motility (2011)
  • Author(s): Takino T, Nagao R, Manabe R, Domoto T, Sekiguchi K, Sato H.
  • Journal Title: FEBS Let Volume: 585 Issue: 21 Pages: 3378-3384
  • DOI: 10.1016/j.febslet.2011.09.039
  • Peer Reviewed
• [Journal Article] GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase (2010)
  • Author(s): Sakr MA, Takino T, Domoto T, Nakano H, Wong RW, Sasaki M, Nakanuma Y, Sato H.
  • Journal Title: Cancer Sci. Volume: 101 Issue: 11 Pages: 2368-2374
  • DOI: 10.1111/j.1349-7006.2010.01675.x
  • NAID: 10027833432
  • Peer Reviewed
• [Journal Article] MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix (2010)
  • Author(s): Takino T, Tsuge H, Ozawa T, Sato H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 3964 Issue: 4 Pages: 1042-1047
  • DOI: 10.1016/j.bbrc.2010.05.059
  • NAID: 120002224339
  • Peer Reviewed
• [Journal Article] Coordinate action of membrane-type matrix metalloproteinase-1(MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion (2010)
  • Author(s): Sato H, Takino T.
  • Journal Title: Cancer Sci Volume: 101 Issue: 4 Pages: 843-947
  • DOI: 10.1111/j.1349-7006.2010.01498.x
  • NAID: 10026590425
  • Peer Reviewed
• [Journal Article] MTl-MMP promotes cell growth and ERK activation through c-Sre and paxillin in three-dimensional collagen matrix. (2010)
  • Author(s): Takino T
  • Journal Title: Biochem. Biophys. Res.Commun. Volume: 364 Pages: 1042-1047
  • Peer Reviewed
• [Journal Article] GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloprotcinase. (2010)
  • Author(s): Sakr MA
  • Journal Title: Cancer Sci. Volume: 101 Pages: 2368-2374
  • Peer Reviewed
• [Journal Article] Coordinate action of membrane-type matrix metalloproteinase-1 (MTl-MMP) and MMP-2 enhances pericellular proteolysis and invasion. (2010)
  • Author(s): Sato H
  • Journal Title: Cancer Sci. Volume: 101 Pages: 843-947
  • Peer Reviewed
• [Journal Article] Coordinate action of membrane-type matrix metalloproteinase-1 (MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion (2010)
  • Author(s): Sato H
  • Journal Title: Cancer Science (印刷中)
  • NAID: 10026590425
  • Peer Reviewed
• [Journal Article] Fascin is involved in tumor necrosis factor (TNF)-α-dependent production of MMP9 in cholaneiocarcinoma (2010)
  • Author(s): Onodera M
  • Journal Title: Lab.Inv. (印刷中)
  • Peer Reviewed
• [Journal Article] Fascin is involved in tumor necrosis factor(TNF)-τ-dependent production of MMP9 in cholangiocarcinoma (2009)
  • Author(s): Onodera M, Zen Y, Harada K, Sato Y, Ikeda H, Itatsu K, Sato H, Ohta T, Asaka M, Nakanuma Y.
  • Journal Title: Lab. Inv. Volume: 89 Issue: 11 Pages: 1261-1274
  • DOI: 10.1038/labinvest.2009.89
  • Peer Reviewed
• [Journal Article] Phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase and nuclear translocation of nuclear factor-kappaB are involved in upregulation of matrix metalloproteinase-9 by tumour necrosis factor-alpha (2009)
  • Author(s): Itatsu K
  • Journal Title: Liver Int. 29 Pages: 291-298
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 is involved in the up-regulation of matrix metalloproteinase-9 in cholangiocarcinoma induced by tumor necrosis factor-alpha (2009)
  • Author(s): Itatsu K
  • Journal Title: Am.J.Pathol. 174 Pages: 829-841
  • Peer Reviewed
• [Presentation] MT1-MMP activates matriptase through the cleavage of its inhibitor HAI-1 (2011)
  • Author(s): 堂本貴寛、滝野隆久、佐藤博
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-04
• [Presentation] MT1-MMP regulates fibronectin assembly (2011)
  • Author(s): 滝野隆久、堂本貴寛、佐藤博
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-04
• [Presentation] Deregulated glycogen synthase kinase(GSK) 3υparticipates in invasion of glioblastoma (2011)
  • Author(s): 近野祐里、中田光俊、滝野隆久、佐藤博, 他10名
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-03
• [Presentation] MT1-MMPによるHAI-1切断を介したセリンプロテアーゼ系の制御 (2011)
  • Author(s): 堂本貴寛、滝野隆久、佐藤博
  • Organizer: 第20回日本がん転移学会総会
  • Place of Presentation: アクトシティー浜松(静岡県)
  • Year and Date: 2011-06-30
• [Presentation] MT1-MMPによる免疫グロブリンファミリー膜タンパクKIM-1の切断 (2011)
  • Author(s): Guo Luyang、滝野隆久、佐藤博
  • Organizer: 第20回日本がん転移学会総会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2011-06-30
• [Presentation] MT1-MMPによるフィブロネクチンの重合と集積抑制 (2011)
  • Author(s): 滝野隆久、堂本貴寛、佐藤博
  • Organizer: 第20回日本がん転移学会総会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2011-06-30
• [Presentation] MT1-MMPによるHAI-1切断を介したセリンプロテアーゼ系の制御 (2011)
  • Author(s): 堂本貴寛
  • Organizer: 第20回日本がん転移学会総会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2011-06-30
• [Presentation] Cleavage of KIM-1 by MT1-MMP (2011)
  • Author(s): Luyang Guo, Takahiro Domoto, Takahisa Takino, Hiroshi Sato.
  • Organizer: 日本分子生物学会第11回春季シンポジウム
  • Place of Presentation: 石川県立音楽堂(石川県)
  • Year and Date: 2011-05-25
• [Presentation] Gi24はMT1-MMPを介したMMP-2活性化を促進することによりがん細胞浸潤を亢進する (2010)
  • Author(s): 佐藤博、堂本貴寛、滝野隆久
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-23
• [Presentation] MT1-MMPによるHAI-1の分解を介したセリンプロテアーゼ系の制御 (2010)
  • Author(s): 堂本貴寛、滝野隆久、佐藤博
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-23
• [Presentation] MT1-MMPは3次元コラーゲン内でc-srcとPaxillinを介してERK活性化と細胞増殖を亢進する (2010)
  • Author(s): 滝野隆久、堂本貴寛、佐藤博
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-23
• [Presentation] Gi24はMT1-MMPを介したMMP-2活性化を促進することによりがん細胞浸潤を亢進する (2010)
  • Author(s): 佐藤博
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際コンベンションセンター(大阪)
  • Year and Date: 2010-09-23
• [Presentation] MT1-MMPによるHAI-1の分解を介したセリンプロテアーゼ系の制御 (2010)
  • Author(s): 堂本貴寛
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際コンベンションセンター(大阪)
  • Year and Date: 2010-09-22
• [Presentation] MT1-MMPは3次元コラーゲン内でc-srcとPaxillinを介してERK活性化と細胞増殖を亢進する (2010)
  • Author(s): 滝野隆久
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際コンベンションセンター(大阪)
  • Year and Date: 2010-09-22
• [Presentation] MT1-MMPによる細胞機能統御 (2010)
  • Author(s): 佐藤博
  • Organizer: 第19回日本がん転移学会総会
  • Place of Presentation: 金沢市文化ホール(石川県) 招待講演
  • Year and Date: 2010-06-17
• [Presentation] MT1-MMPによるセリンプロテアーゼ系の制御 (2010)
  • Author(s): 堂本貴寛
  • Organizer: 第19回日本がん転移学会総会
  • Place of Presentation: 金沢敵化ホール(石川県)
  • Year and Date: 2010-06-17
• [Presentation] MT1-MMPによる細胞機能統御 (2010)
  • Author(s): 佐藤博
  • Organizer: 第19回日本がん転移学会総会
  • Place of Presentation: 金沢市文化ホール(石川県)
  • Year and Date: 2010-06-16
• [Presentation] MT1-MMPによる細胞増殖誘導機構 (2010)
  • Author(s): 長尾亮太、滝野隆久、佐藤博
  • Organizer: 第19回日本がん転移学会総会
  • Place of Presentation: 金沢市文化ホール(石川県)
  • Year and Date: 2010-06-16
• [Presentation] MT1-MMPによるセリンプロテアーゼ系の制御 (2010)
  • Author(s): 堂本貴寛、滝野隆久、佐藤博
  • Organizer: 第19回日本がん転移学会総会
  • Place of Presentation: 金沢市文化ホール(石川県)
  • Year and Date: 2010-06-16
• [Presentation] Overview of Metastatic Research and Roles of MT1-MMP in Tumor Invasion and Metastasis (2009)
  • Author(s): Sato H.
  • Organizer: International Symposium to Commemorate the 50th Anniversary of Osaka Medical Center for Cancer & Cardiovascular Diseases
  • Place of Presentation: 大坂国際交流センター(大阪府)
  • Year and Date: 2009-11-14
• [Presentation] MT1-MMPによる浸潤性増殖誘導 (2009)
  • Author(s): 滝野隆久、佐藤博
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] MT1-MMPによる浸潤性増殖誘導 (2009)
  • Author(s): 滝野隆久
  • Organizer: 第82回 日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド (兵庫県)
  • Year and Date: 2009-10-22
• [Presentation] MT1-MMPによる浸潤性増殖誘導 (2009)
  • Author(s): 滝野隆久
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
  • Year and Date: 2009-10-03
• [Presentation] MT1-MMPによる浸潤性増殖誘導 (2009)
  • Author(s): 滝野隆久、佐藤博
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-02
• [Presentation] 膜型セリンプロテアーゼによる膜型MMP活性化機構の解析 (2009)
  • Author(s): 堂本貴寛
  • Organizer: 第18回 日本がん転移学会
  • Place of Presentation: 旭川グランドホテル (北海道)
  • Year and Date: 2009-07-23
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/department/cb/04.html