Investigation of the role of histone reader in cancer stem cells and application of its inhibition to modulate differentiation ability of cancer stem cells
| Project/Area Number |
17K07190
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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 biology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Hattori Naoko 国立研究開発法人国立がん研究センター, 研究所, 研究員 (30611090)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | エピジェネティクス / ヒストン修飾 / がん幹細胞 |
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| Outline of Final Research Achievements |
In this study, to develop therapeutic strategy for cancer stem cells by targeting histone reader, we explored the role of human CDYL2 in cancer stem cells (CSCs). Expression of exogenous CDYL2 increased the CSC population in two breast and three colorectal cancer cell lines, and upregulated genes involved in cancer invasion and cancer metastasis. On the other hand, CDYL2-knock-out decreased CSC population in colorectal cancer cells, and its reduction was cancelled by CDYL2-rescue. The effect of CDYL2 expression on drug sensitivity was also investigated. In breast cancer cells with CDYL2-overexpression, the sensitivity to 5-FU was significantly decreased, and in CDYL2-knock-out colorectal cancer cells, the sensitivities to 5-FU and irinotecan were enhanced, indicating the possibility of a combination therapy of CDYL2 inhibitor and cytotoxic drugs. These data demonstrate that CDYL2 is important for maintenance of cancer stem cells.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒストンリーダーは、ヒストン修飾を認識後、クロマチン構造変換を誘導して遺伝子の発現を調節し、エピジェネティック情報を細胞の表現系へ変換する重要な因子である。本研究によって、ヒストンリーダーによるがん幹細胞性の制御メカニズムが解明される。また、その阻害による「がん幹細胞の分化制御」によるがん治療の可能性が広がる。さらに、がん幹細胞を死滅させるのではなく、休止状態に保つことで、がん組織自体の増大を押さえて共存する「がん幹細胞休眠療法」の概念を提唱できる。
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Report
(4 results)
Research Products
(10 results)
