| Project/Area Number |
25860206
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
HONGU Tsunaki 筑波大学, 医学医療系, 助教 (30628920)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 腫瘍血管新生 / Arf6 / 細胞接着 / 肝細胞増殖因子 |
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| Outline of Final Research Achievements |
In this study, we found that Arf6 regulates tumor neoangiogenesis induced by hepatocyte growth factor (HGF), but not other angiogenic factors, by utilizing endothelial cell-specific Arf6 conditional knockout mice. In Arf6 deficient endothelial cells, HGF-stimulated beta1 integrin recycling was abolished, resulting in inhibition of spreading, migration and focal adhesion formation. This function of Arf6 was regulated by its guanine nucleotide exchange factor Grp1. Finally, the pharmacological inhibition of Grp1-Arf6 axis efficiently suppressed tumor vascularization. Taken together, our findings shed the light on the mechanism of angiogenesis regulated by HGF, and provide evidence for an important role of Arf6 in tumor vascularization.
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