| Project/Area Number |
22650230
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Tumor biology
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| Research Institution | 公益財団法人がん研究会 (2011)
Japanese Foundation For Cancer Research (2010) |
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Principal Investigator |
SEIMIYA Hiroyuki 公益財団法人がん研究会, がん化学療法センター分子生物治療研究部, 部長 (50280623)
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| Co-Investigator(Kenkyū-buntansha) |
MIGITA Toshiro がん研究会, がん化学療法センター分子生物治療研究部, 研究員 (20462236)
MASHIMA Tetsuo がん研究会, がん化学療法センター分子生物治療研究部, 研究員 (30311228)
|
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| Co-Investigator(Renkei-kenkyūsha) |
TAGUCHI Ryo 中部大学, 大学院・生命健康科学研究科, 教授 (20080210)
SAITO Shinichi 東京理科大学, 理学部・第一化学科, 教授 (80283076)
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| Project Period (FY) |
2010 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥3,320,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | 脂質代謝 / 細胞増殖 / がん / 微小環境 / メタボローム / ATP-クエン酸リアーゼ / 活性酸素 / 酸化ストレス / 脂質 / バイオマーカー / 細胞死 |
|---|
| Research Abstract |
Cancer cells often enhance de novo lipid synthesis. However, its functional significance remains unknown. In this study, we found that depletion of a lipid-synthesizing enzyme, called ATP citrate lyase(ACLY), blocks cancer cell growth. This anticancer effect was more evident in those cells with lower reactive oxygen species(ROS) and lower phosphorylation level of AMPK. ACLY depletion elevated the relative abundance of palmitate. Because palmitate can induce ROS, it may contribute to the anticancer effect of ACLY depletion. In clinical colon tumors, higher malignant grades correlated with lower levels of AMPK phosphorylation and oxidative stress, suggesting that ACLY inhibition can be utilized as an anticancer therapeutics.
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