| Project/Area Number |
18K15235
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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 |
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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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | トリプルネガティブ乳癌 / 上皮間葉転換 / TNBC / EMT / MET / 乳癌 / Basal-like breast cancer / 上皮間葉転換(EMT) / トリプルネガティブ乳癌(TNBC) / CRISPR-Cas9 Screening |
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| Outline of Final Research Achievements |
Epithelial-mesenchymal transition (EMT) and its reverse process, MET, are crucial in several stages of cancer metastasis. Spatiotemporally-coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human TNBC cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio. First, we established EMT-reporter cells which have E-cadherin-promoter driven mKO2 and vimentin-promoter driven EGFP. Next, we tried to analyze the effect of CRISPR/Cas9-mediated gene knockout on EMT/MET plasticity. Results showed that mesenchymal population in HCC38 cells was significantly decreased or increased by gene knockout using gRNAs for ZEB1 or miR200c, respectively. In this study, we performed CRISPR/Cas9-mediated genome-wide screening to identify novel mechanisms for EMT-MET plasticity in triple-negative breast cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
乳癌は外科的切除により予後が大きく改善する癌腫であるものの、現在でもTNBCなどでは転移が起きてしまうと予後を改善することは難しい。この転移を予防・治療するためにはその根本的な機構を解明する必要がある。上皮間葉転換(EMT)は転移や再発に重要な機構であるが、腫瘍内におけるEMTとその逆反応METの平衡関係を決定する機構はいまだによくわかっていない。本研究では転移を標的とした治療法開発を目的としてその機構の一端を明らかにした。
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