Analysis of a molecular mechanism by which JNK-binding proteins regulate turnover of focal adhesions and formAnalysis of a molecular mechanism by which JNK-binding proteins regulate turnover of focal adhesions and formation of cell polarity
| Project/Area Number |
18590287
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
TAKINO Takahisa Kanazawa University, Cancer Research Institute, Associate Professor (40322119)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cancer / Invasion / Cell migration / MAPK / JNK / ERK / MT1-MMP / ECM / 情報伝達 / インテグリン |
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| Research Abstract |
Membrane-type 1 matrix metalloproteinase (MT1-MMP) has been implicated in tumor invasion and metastasis. We previously reported that extracellular matrix degradation by MT1-MMP regulates cell migration via modulating sustained integrin-mediated signals. In this study, MT1-MMP-expressing cells were plated onto fibronectin-coated plates and monitored for cell-matrix adhesion formation and fibronectin degradation. The fibronectin was degraded and removed in line with the cell migration track. The migrating cells showed a polarized morphology and were in contact with the edge of fibronectin through the leading edge in which cell-matrix adhesions are concentrated. Expression of MT1-MMP targeted to cell-matrix adhesions by fusing with the focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK) promoted the initial fibronectin lysis at the cell periphery immediately after adhesion. These results suggest that fibronectin is degraded by MT1-MMP located at cell-matrix adhesions which are concentrated at the leading edge of the migrating cells. lb inhibit MT1-MMP at cell-matrix adhesion, the dominant negative form of MT1-MMP (MT1-Pex) was targeted to the cell-matrix adhesion by fusing with the FAT domain (MT1-Pex-FAT). MT1-Pex-FAT accumulated at cell-matrix adhesions and inhibited fibronectin degradation as well as FAK phosphorylation more effectively than parental MT1-Pex. MT1-Pex-FAT was also shown to suppress the invasion of tumor cells into 3-dimensional collagen gel more strongly than MT1-Pex. These results suggest that MT1-MMP-mediated extracellular matrix lysis at cell-matrix adhesions induces the establishment of cell polarity, which facilitates cell-matrix adhesion turnover and subsequent cell migration. This model highlights the role of MT1-MMP at the leading edge of migrating cells.
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] Cleavage of growth differentiation factor 15 (GDF15) by membrane type I-matrix metalloproteinase abrogates GDF15-mediated suppression of tumor cell growth2007
Author(s)
Abd, El-Aziz, S., H., Endo, Y., Miyamaori, H., Takino, T., Sato, H
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Journal Title
Cancer Science 98
Pages: 1330-5
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Regulation of N-cadherin- based cell-cell interaction by JSAP1 scaffold in PC12h cells2007
Author(s)
Bayarsaikhan, M., Takino, T., Gantulga, D., Sato, H., Ito, T., Yoshioka, K
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Journal Title
Biochem. Biophys. Res. Commun 353
Pages: 357-362
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Membrane-type 1 matrix metalloproteinase modulates focal adhesion stability and cell migration2006
Author(s)
Takino, T., Watanabe, Y., Matsui, M., Miyamori, H., Kudo, T., Seiki, M., Sato, H.
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Journal Title
Exp. Cell Res 312
Pages: 1381-1389
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Cleavage of amyloid-precursor protein (APP) by membrane-type matrix metalloproteinases2006
Author(s)
Ahmad, M., Takino.T., Miyamori, H., Yoshizaki, T., Furukawa, M., Sato, H
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Journal Title
J. Biochem 139
Pages: 517-526
Description
「研究成果報告書概要(欧文)」より
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