| Project/Area Number |
18K15078
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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 49020:Human pathology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | MELF / SDPR / ALDH1 / MELF pattern / 類内膜癌 |
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| Outline of Final Research Achievements |
Endometrioid carcinoma (EC) is one of the most common malignancies of the female genital system. We reported previously that aldehyde dehydrogenase 1 (ALDH1) is related to the tumorigenic potential of EC. We compared the levels of various proteins in human EC cells with high and low ALDH1 expression and found that serum deprivation-response protein (SDPR) was preferentially expressed in cells with high ALDH1 expression. Using SDPR knockout EC cells generated using the CRISPR/Cas9 system, we revealed that SDPR was correlated with invasion, migration, the epithelial-mesenchymal transition (EMT) and colony formation, as well as the expression of ALDH1. RNA-sequencing showed that integrin-linked kinase (ILK) signaling is involved in the effect of SDPR on ALDH1. Immunocytochemical analysis revealed that the localization of ILK at the cell cortex was disrupted by SDPR knockout, potentially interfering with ILK signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、子宮体部類内膜癌培養細胞においてSDPRがILKのシグナル伝達を介してALDH発現を制御していることが示唆された。また病理組織標本を用いた免疫染色においてもSDPRはMELF patternを含む高い浸潤能と関連していた。SDPRはcaveolaeを媒介する多数のシグナルに関連していると考えられ、正常細胞への影響に伴う副作用という観点からは、SDPR自体を治療標的とすることは難しいが、ILKシグナルは治療標的として有望である。ILKシグナルの上流、下流に存在する因子を同定し、ALDH発現を制御することは、通常の治療に抵抗性の類内膜癌に対する新たな薬物の開発につながると考える。
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