| Project/Area Number |
24300329
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kanazawa University |
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Principal Investigator |
MATSUMOTO Kunio 金沢大学, がん進展制御研究所, 教授 (90201780)
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| Co-Investigator(Renkei-kenkyūsha) |
SAKAI Katsuya 金沢大学, がん進展制御研究所, 助教 (10523318)
NAKAMURA Takahiro 金沢大学, がん進展制御研究所, 助教 (70414018)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | 細胞増殖因子 / 転移 / 薬剤耐性 / HGF / Met / 浸潤 / 人工アゴニスト / 環状ペプチド / がん細胞 / エピジェネティクス / PRC / MMP |
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| Outline of Final Research Achievements |
Tumor invasion, a typical characteristic of malignant tumors, is regulated not only by intrinsic gene expression profile but also extracellular factors. Met activation by HGF participates in tissue regeneration and tumor invasion. We here found that 1) aberrant proteasome-mediated proteolysis in PRC complex participates in activation of genes (e.g., MMP-2) involved in acquisition of 3-D invasiveness in human malignant mesothelioma cells, and 2) Met expression is regulated by hierarchal equilibrium between Met-low and Met-high populations in malignant melanoma cells, by which invasive and metastatic characteristics is conferred. Based on background for HGF-Met protein-protein interactions, Met-binding cyclic peptides were obtained by RaPID system, and the dimerized peptides induced Met activation and Met-mediated biological responses, in indistinguishable ability to HGF. Thus, we succeeded in generation of artificial Met-agonist / artificial HGF composed of macrocyclic peptide.
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