| Project/Area Number |
15K15086
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 慢性炎症 / インスリン抵抗性 |
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| Outline of Final Research Achievements |
Excessive nutrition gives rise to noninfectious inflammation, a major component of metabolic syndrome, but the molecular mechanism by which nutrient signalling triggers inflammation has remained poorly understood. Here we show that the transcription factor forkhead box K1 (FOXK1) links nutrient signaling mediated by mammalian target of rapamycin complex 1 (mTORC1) to inflammation. FOXK1 was dephosphorylated in response to mTORC1 activation, and such dephosphorylated FOXK1 directly induced expression of CCL2, an inflammatory chemokine. The mTORC1-FOXK1-CCL2 pathway was found to be integral to infiltration of tumor-associated macrophages (TAMs) that support tumor growth. Depletion of FOXK1 in tumor cells thus attenuated TAM infiltration and tumor growth in mice in a manner similar to rapamycin treatment. Our results suggest that FOXK1 plays a central role in nutrient signalling to noninfectious inflammation.
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