| Project/Area Number |
15K06874
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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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| Research Field |
Tumor therapeutics
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原田 大志 九州大学, 大学病院, 助教 (10380619)
中西 洋一 九州大学, 大学病院, 教授 (20172356)
岩間 映二 九州大学, 医学研究院, 助教 (40567343)
田中 謙太郎 九州大学, 医学(系)研究科(研究院), 助教 (00536849)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | CD44バリアント(CD44v) / 活性酸素 / 上皮成長因子受容体(EGFR) / 非小細胞肺癌 / グルタチオン / 抗癌剤感受性 / レドックスバランス / EGFR遺伝子変異 / ROS / CD44 / 肺癌 / EGFR遺伝子 / 癌幹細胞 |
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| Outline of Final Research Achievements |
Activating mutations of the epidermal growth factor receptor gene (EGFR) are oncogenic drivers in non-small cell lung cancer (NSCLC), but it has remained unknown whether ligand-independent EGFR signaling conferred by EGFR mutation triggers reactive oxygen species (ROS) generation in NSCLC cells. We showed EGFR signaling due to EGFR mutation increased ROS levels. The expression of CD44v isoforms was found to be inversely correlated with basal ROS levels in EGFR-mutated NSCLC cell lines. Knockdown of CD44v induced depletion of intracellular glutathione (GSH) and increased ROS levels in EGFR-mutated NSCLC cells that express CD44v at a high level (CD44vhigh). In addition, depletion of GSH enhanced the cytotoxicity of cisplatin in CD44vhigh EGFR-mutated NSCLC cells. Knockdown of CD44v also enhanced cisplatin cytotoxicity in CD44vhigh EGFR- mutated NSCLC cells. Our results thus implicate CD44v in redox adaptation and as a potential target for treatment in CD44vhigh EGFR-mutated NSCLC cells.
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