2020 Fiscal Year Final Research Report
The study for the role of NFE2L2 on cell invasion in malignant melanomas.
| Project/Area Number |
18K07022
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | メラノーマ / NFE2L2経路 / PGC1alpha経路 / 細胞浸潤機構 |
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| Outline of Final Research Achievements |
Here, we have investigated the relationship between the PGC1alpha and NFE2L2 pathways in malignant melanoma cell lines. Vemurafenib, a BRAF inhibitor, has been shown to inhibit cell invasion via the PGC1alpha pathway in malignant melanoma harboring the V600E mutation in the BRAF gene. We have found that disruption of the NFE2L2 pathway inhibited the invasive activity of a cell line on which vemurafenib had no inhibitory effect. We also confirmed that the transcription factor BACH1 induced via the NFE2L2 pathway was involved in the mechanism. These findings suggest that the PGC1alpha and NFE2L2 pathways control cell invasion independently, and that inhibition of the NFE2L2 pathway may also be a promising approach for inhibiting the invasion of malignant melanomas for which vemurafenib is not effective.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
浸潤能、すなわち転移能の獲得は、メラノーマの腫瘍生物学的特徴の一つであり大きな臨床治療上の大きな問題でもある。本研究の学術的な意義は、NFE2L2の非悪性腫瘍と悪性腫瘍において浸潤機構における位置付けが異なる可能性、さらに、同一のメラノーマで複数の独立した浸潤制御系が存在する可能性を示した点である。また社会的意義としては、ベムラフェニブが奏効しない多くのメラノーマの治療標的として、NFE2L2からBACH1へ至る経路に存在する因子が標的となりうる可能性を示した点である。
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