Development of a novel therapeutic approach targeting the processing of angiopoietin-like protein 2 for suppressing of tumor metastasis
Project/Area Number |
15K20008
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Orthopaedic surgery
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Research Institution | Kumamoto University (2016) Teikyo University (2015) |
Principal Investigator |
Odagiri Haruki 熊本大学, 生命資源研究・支援センター, 客員助教 (60732740)
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | がん / ANGPTL2 / プロセシング / TLL1 / 低分子化合物 / がん抑制遺伝子 |
Outline of Final Research Achievements |
Here, we show that TLL1 (tolloid-like 1) predominantly contributes to the processing of ANGPTL2 among BMP-1 (bone morphogenic protein-1)/TLD (tolloid) family proteins. In addition, we found that secreted ANGPTL2 proteins are O-glycosylated in the conditioned medium of human tumor cell lines. We also identified an O-glycosylation site of ANGPTL2 protein and showed that ANGPTL2 proteins containing the mutated O-glycosylation site exhibit increased susceptibility to cleavage by TLL1. These results suggest that O-glycosylation of ANGPTL2 protein is important for protection from cleavage by TLL1. Therefore, not only promoting the activity and expression of TLL1, but also suppressing the O-glycosylation of ANGPTL2 protein in tumor cells may be a novel therapeutic approach for ANGPTL2 signaling-mediated tumor metastasis.
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Report
(3 results)
Research Products
(2 results)
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[Journal Article] Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity2016
Author(s)
Yugami M, Odagiri H, Endo M, Tsutsuki H, Fujii S, Kadomatsu T, Masuda T, Miyata K, Terada K, Tanoue H, Ito H, Morinaga J, Horiguchi H, Sugizaki T, Akaike T, Gotoh T, Takai T, Sawa T, Mizuta H, Oike Y
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Journal Title
Journal of Biological Chemistry
Volume: 291
Issue: 36
Pages: 18843-18852
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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