| Project/Area Number |
24590390
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SHIBANUMA Motoko 昭和大学, 薬学部, 教授 (60245876)
ISHIKAWA Fumihiro 昭和大学, 薬学部, 助教 (60515667)
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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 |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 足場非依存性増殖 / がん転移抑制 / HIC-5 / 足場非依存性増殖能 |
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| Outline of Final Research Achievements |
In the present study, we addressed HIC-5-dependent growth arrest mechanism under nonadherent conditions. The mechanism transcriptionally induced a CDK inhibitor (CKI), p21Cip1, in response to disruption of cell-ECM interactions. The role of HIC-5 in this mechanism was to tether KLF4, a transcription factor essential for transactivation of p21Cip1, to DNA sites in response to cellular detachment.
We also found that MMP-9 expression was upregulated by depletion of HIC-5 with RNAi, which potentially contributes to HIC-5-mediated regulation of tumor metastasis in vivo. Interestingly, ectopic expression of kinase-inactivated TGF-b type I receptor completely blocked the HIC-5 effect. Neither Smads phosphorylation nor expression of other TGF-b-targeted genes were affected by HIC-5 levels. Collectively, a new TGF-b signaling pathway has emerged contributing to cancer progression through the regulation of MMP-9 expression depending on HIC-5.
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