Functional analysis of DCLK1 in pulmonary cancer associated with IPF
| Project/Area Number |
18K15059
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MARUYAMA Junichi 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (30723639)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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)
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| Keywords | 特発性肺線維症 / DCLK1 / NF-κB / DNA損傷修復 / 肺がん / DNA修復 |
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| Outline of Final Research Achievements |
Idiopathic pulmonary fibrosis (IPF) is frequently associated with lung cancer. However, the molecular mechanism underlying this association remains unclear. We analyzed the gene expression profiles of IPF lungs using public datasets and extracted 94 genes that were upregulated in all of them. Among these, we identified DCLK1, a well-known cancer stem cell-marker. In this study, we confirmed that DCLK1 expression was enhanced in human IPF lungs and in lungs of mice with bleomycin-induced fibrosis. We also found that the human lung cancer H1299 cells expressed DCLK1 when exposed to the conditioned medium derived from the LPS-stimulated macrophage-like RAW264.7 cells. We also revealed that IL-17 and LTA induced DCLK1 expression in human lung cancer H1299 cells. Moreover, RelB silencing, but not RelA silencing, blocked the induction of DCLK1 expression by conditioned medium. Hence, the inhibition of alternative NF-κB signaling may be useful to prevent cancer development in IPF lungs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果は、IPF肺においては浸潤するマクロファージなどの炎症性細胞から分泌されるサイトカインにより、肺胞上皮細胞においてalternative NF-κB経路が活性化され、その結果癌幹細胞性が確立して発癌に至るというモデルを支持する。このモデルが正しければ、alternative NF-κB経路を阻害すればIPFに併発する肺癌発癌を予防できる可能性が期待される。
本研究はIPF肺を対象とした。しかし、肺以外の臓器でも慢性的な炎症に伴い、alternative NF-κB経路の活性化とそれに伴うDCLK1発現誘導がなされ、発癌に繋がっている可能性があると考えている。
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Report
(4 results)
Research Products
(3 results)
