| Project/Area Number |
26830078
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | mTORC1 / CCL2 / がん / マクロファージ / mTOR / FOXK1 / 炎症 |
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| Outline of Final Research Achievements |
Myeloid-derived suppressor cells and tumor-associated macrophages accumulate to tumor sites and construct tumor microenvironment, which promote immune suppression and tumor progression. The accumulation of the myeloid cells is known to be dependent on tumor cell-derived chemokine CCL2. The overexpression of CCL2 is clinically observed in various types of tumor. However, it is poorly understood how CCL2 is upregulated in tumor cells. Here, we show that CCL2 transcription is regulated by mammalian target of rapamycin complex 1, which is frequently activated in downstream of PI3K/AKT pathway in tumor cells. The mTORC1-dependent CCL2 expression is mediated by dephosphorylation of transcription factor FOXK1. Blocking mTORC1-FOXK1 axis prevents CCL2-dependent accumulation of myeloid cells and tumor progressions. These results provide a molecular mechanism bridging from tumor initiation to constructing tumor microenvironment.
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