| Project/Area Number |
19K16735
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Raja Erna 東京大学, 大学院医学系研究科(医学部), 特任研究員 (30770581)
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| Project Period (FY) |
2019-04-01 – 2020-03-31
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| Project Status |
Discontinued (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | BMP / glioblastoma / apoptosis / EPHA6 |
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| Outline of Research at the Start |
Although BMP acts as an inhibitor for glioblastoma progression in various pre-clinical models, its therapeutic application is not yet been achieved. We propose that one of EPHA receptor tyrosine kinases is a factor that could confer sensitivity to BMP-induced apoptosis and its high expression is correlated with better prognosis. Our data will identify factor(s) that sensitizes cells towards BMP-induced apoptosis, which may be useful as biomarker for selection of BMP-based therapy.
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| Outline of Annual Research Achievements |
EPHA6 sensitized glioblastoma cells for BMP-2-induced apoptosis. Inoculation of cells pre-treated with BMP-2 and EPHA6 over-expression into nude mice brain showed tumor suppression leading to longer survival, in agreement with TCGA patient data analysis.
The cooperative effect on apoptosis induction depended on the kinase activity of BMP type I receptor but was independent of EPHA6 kinase function, as tested using EPHA6 kinase inactive mutant K757R and BMP receptor inhibitor LDN193189. EPHA6 also formed a protein complex with ALK-2 BMP receptor.
Finally, RNA-sequencing results suggested that apoptosis-associated genes are up-regulated in EPHA6 over-expressing cells with potentially important downstream target genes for further study. The manuscript has been submitted and is being revised.
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