2014 Fiscal Year Final Research Report
Functional analysis of small GTPase Arf6 in pathological angiogenesis
| 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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| Keywords | 腫瘍血管新生 / Arf6 |
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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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| Free Research Field |
腫瘍血管新生
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