2014 Fiscal Year Final Research Report
Role of ephrin-A1 in lung metastasis
| Project/Area Number |
25870760
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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
Respiratory surgery
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 転移 / Eph / ephrin / ADAM |
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| Outline of Final Research Achievements |
It has been reported that overexpression of ephrin-A1 is positively correlated with prognosis in various cancers such as hepatocellular carcinoma. However, the detailed function remains unclear. Therefore, I focused on metastasis that get worse their prognosis in cancer patients and analyzed functions of ephrin-A1 in lung metastasis. I found that ADAM12 identified as a proteinase against ephrin-A1, cleaved ephrin-A1 in primary tumors, and the the serum level is increased. Activated EphA2 by cleaved ephrin-A1 is immediately endocytosed and undergone proteolysis and therby localization of VE-cadherin at the plasma membrane is lost. As a result of destabilization of EphA2 and VE-cadherin at the plasma membrane in lung vascular endothelial cells leads to hyper-permeability and enhances lung metastasis. A neutralizing antibody against ephrin-A1 is effective for lung metastasis. I would like to develop anti-ephrin-A1 therapeutic drugs.
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| Free Research Field |
分子生物学
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