2020 Fiscal Year Final Research Report
Elucidation of a new mechanism for controlling glioblastoma growth focusing on lipid metabolism and histone demethylase LSD1
Project/Area Number |
19K18434
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Kagoshima University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Keywords | 膠芽腫 / 脂質代謝 / EGFR / LSD1 |
Outline of Final Research Achievements |
In glioblastoma cells, we confirmed that LSD1 protein is regulated by the activity of EGFR signaling, which is involved in tumor growth (its activation increases LSD1 protein). Inhibition of LSD1 in glioblastoma cells with activated EGFR signaling resulted in the depletion of intracellular cholesterol, and when the concentration of lipid supplement was adjusted along with LSD1 inhibition in the culture, the number of dead cells increased at lower concentrations. In contrast, inhibition of LSD1 in normal astrocytes induced expression of genes in cholesterol synthesis more strongly than in glioblastoma cells, suggesting that they may be more resistant to LSD1-induced intracellular cholesterol depletion.
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Free Research Field |
脳神経外科学分野
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Academic Significance and Societal Importance of the Research Achievements |
膠芽腫は最も予後の悪いがんの一つであり、様々な治療の開発でも生存期間は中央値15ヵ月程度とあまり改善しておらず、新たな治療法が求められている。近年、様々な分子標的薬が多くのがんで治療成績を向上させ、EGFR活性を阻害する薬剤はEGFR遺伝子に変異をもつ肺がんの生存期間を延長させた。多くの膠芽腫でもEGFRは活性化しているが、脳には血液脳関門というバリア機構のため多くの薬剤が通過できず、既存の分子標的薬では効果が十分でない。本研究からLSD1がEGFRシグナルの下流で膠芽腫の生存に関わる脂質代謝を調節しており、LSD1はEGFRシグナルが活性化した膠芽腫の治療標的となり得ることが示唆された。
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