2015 Fiscal Year Final Research Report
Mechanistic insights of tumor promotion via a novel mTOR signaling pwthway
| 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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| Keywords | mTORC1 / CCL2 / がん / マクロファージ |
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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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| Free Research Field |
シグナル伝達
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