| Project/Area Number |
19390092
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East |
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Principal Investigator |
ARAKAWA Hirofumi National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, 生物物理部, 部長 (70313088)
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| Project Period (FY) |
2007 – 2008
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| Project Status |
Completed (Fiscal Year 2008)
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| Budget Amount *help |
¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 分子腫瘍学 / ネトリン / ネトリンレセプター / アポトーシス / 細胞死 / p53 / 細胞死抑制 / カスペース / 神経軸索誘導 |
|---|
| Research Abstract |
In the present study, we identified a novel netrin-1 receptor X that mediates netrin-1 regulated anti-cell death activity. The interaction of netrin-1 with receptor X not only blocked p53-dependent apoptosis but also induced chemotaxis of both vascular endothelial cells and cancer cells. The interaction led to activation of AKT and Src. In vivo, netrin-1 was colocalized with receptor X at the basement membrane of colorectal epithelial cells. Netrin-1 expression was frequently lost in human colorectal cancer tissues whereas the expression was elevated in cancer stromal region. In 3D culture experiment, the interaction of netrin-1 with receptor X induced cell polarization and growth suppression of colorectal cancer cells. These results suggest that the signaling pathway via netrin-1 and receptor X plays a critical role in cell polarity to suppress tumor initiation and progression.
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