A molecular mechanism that regulates extracellular matrix degradation and cell polarity in migrating cells.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590356
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kanazawa University
• Principal Investigator: TAKINO Takahisa 金沢大学, がん進展制御研究所, 准教授 (40322119)
• Project Period (FY): 2011-04-28 – 2014-03-31
• Keywords: 細胞運動 / 浸潤 / ECM / MMP

Research Abstract

We have shown that membrane-type 1 matrix metalloproteinase (MT1-MMP) regulate fibronectin (FN) assembly by cleaving it, which results in promotion of cell motility and proliferation. FN matrix assembly requires the increased cytoskeletal tension generated by cadherin adhesions. In a co-culture of Rat1 fibroblasts and MT1-MMP-silenced but not control HT1080 cells, FN fibrils extended from Rat1 to cell-matrix adhesions in HT1080 cells, and N-cadherin adhesions were formed between these cells. MT1-MMP knockdown promoted FN matrix assembly and N-cadherin adhesions in HT1080 cells, which was abrogated by double knockdown with either integrin beta1 or FN. Conversely, inhibition of N-cadherin adhesions suppressed FN matrix formation in MT1-MMP-silenced cells. These data demonstrate that FN assembly initiated by MT1-MMP knockdown results in increased N-cadherin adhesions, which are prerequisite for further FN matrix formation.

Research Products

• [Journal Article] Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival (2013)
  • Author(s): Teng L, Nakada M, Furuyama N, Sabit H, Furuta T, Hayashi Y, Takino T, Dong Y, Sato H, Sai Y, Miyamoto KI, Berens ME, Zhao SG, Hamada JI
  • Journal Title: Neuro-Oncology Volume: 15 Pages: 1710-1720
  • DOI: 10.1093/neuonc/not128
  • Peer Reviewed
• [Journal Article] MT1-MMP prevents growth inhibition by three dimensional fibronectin matrix (2013)
  • Author(s): Takino T, Guo L, Domoto T, Sato H
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 436 Pages: 503-508
  • DOI: 10.1016/j.bbrc.2013.05.134
  • Peer Reviewed
• [Journal Article] Integrinα3 is overexpressed in glioma stem-like cells and promotes invasion (2013)
  • Author(s): Nakada M, Nambu E, Furuyama N, Yoshida Y, Takino T, Hayashi Y, Sato H, Sai Y, Tsuji T, Miyamoto KI, Hirao A, Hamada JI
  • Journal Title: Br itish J our nal of Cancer Volume: 108 Pages: 2516-2524
  • DOI: 10.1038/bjc.2013
  • Peer Reviewed
• [Journal Article] Aberrant glycogen synthase kinase 3βis involved in pancreatic cancer cell invasion and resistance to therapy (2013)
  • Author(s): Kitano A, Shimasaki T, Chikano Y, Nakada M, Hirose M, Higashi T, Ishigaki Y, Endo Y, Takino T, Sato H, Sai Y, Miyamoto K, Motoo Y, Kawakami K, Minamoto T
  • Journal Title: PLoS One Volume: 8 Pages: e55289
  • DOI: 10.1371/journal.pone.0055289
  • Peer Reviewed
• [Journal Article] Shedding of kidney injury molecule-1 by membrane-type 1 matrix metalloproteinase (2012)
  • Author(s): Guo L, Takino T, Endo Y, Domoto T, Sato H
  • Journal Title: J our nal of Biochemistry Volume: 152 Pages: 425-432
  • DOI: 10.1093/jb/mvs082
  • Peer Reviewed
• [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 LY, Sato H
  • Journal Title: Cancer Science Volume: 103 Pages: 448-454
  • DOI: 10.1111/j.1349-7006.2011.02162.x
  • Peer Reviewed
• [Journal Article] Membrane-type 1 matrix metalloprotease 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 Letter s Volume: 585 Pages: 3378-.384
  • DOI: 10.1016/j.febslet.2011.09.039
  • Peer Reviewed
• [Presentation] MT1-MMPは3次元フィブロネクチンマトリックス由来の増殖抑制を回避する (2013)
  • Author(s): 滝野隆久, 佐藤博
  • Organizer: 第72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: 2013-10-02
• [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22回日本がん転移学会学術総会
  • Place of Presentation: ホテルブエナビスタ松本(長野県)
  • Year and Date: 2013-07-11
• [Presentation] HAI-1分解を介するセリンプロテアーゼ系の活性化は腫瘍細胞の遊走と浸潤能を亢進する (2012)
  • Author(s): 堂本貴寛, 滝野隆久, 源利成, 佐藤博
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-20
• [Presentation] MT1-MMPによるN-カドヘリン接着制御 (2012)
  • Author(s): 滝野隆久, 堂本貴寛, 佐藤博
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-20
• [Presentation] MT1-MMPによるHAI-1切断は細胞運動・浸潤に係るセリンプロテアーゼを活性化する (2012)
  • Author(s): 佐藤博, 滝野隆久
  • Organizer: 第21回日本がん転移学会学術総会
  • Place of Presentation: オリエンタルホテル広島(広島県)
  • Year and Date: 2012-07-13
• [Presentation] MT1-MMPによるN-カドヘリン接着の制御 (2012)
  • 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学術総会
  • Place of Presentation: オリエンタルホテル広島(広島県)
  • Year and Date: 2012-07-13
• [Presentation] MT1-MMPはHAI-1を切断することでMatriptaseを活性化する (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] Glycogen synthase kinase (GSK) 3βは膠芽腫の浸潤を促進する (2011)
  • Author(s): 近野祐里, 中田光俊, 廣瀬まゆみ, 北野綾子, 宮下勝吉, 藤沢弘範, 林裕, 滝野隆久, 佐藤博, 崔吉道, 宮本謙一, 川上和之, 源利成
  • 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によるファイ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学術総会
  • 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, 滝野隆久, 佐藤博
  • Organizer: 第20回日本がん転移学会学術総会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2011-06-30
• [Presentation] MT1-MMPによるファイブロネクチン重合制御
  • Author(s): 滝野隆久, 堂本貴寛, 佐藤博
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/department/cb/04.html