論文 - 詳細
| RRC ID | 56703 |
|---|---|
| 著者 | Nakatsumi H, Matsumoto M, Nakayama KI. |
| タイトル | Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages. |
| ジャーナル | Cell Rep |
| Abstract |
C-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)-κB signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1) but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1. Activation of mTORC1 induces dephosphorylation of FOXK1, resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-κB and that CCL2 produced by this pathway contributes to tumor progression. |
| 巻・号 | 21(9) |
| ページ | 2471-2486 |
| 公開日 | 2017-11-28 |
| DOI | 10.1016/j.celrep.2017.11.014 |
| PII | S2211-1247(17)31634-0 |
| PMID | 29186685 |
| MeSH | Animals Chemokine CCL2 / metabolism* Female Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism* Gene Expression Regulation / genetics Gene Expression Regulation / physiology HCT116 Cells Humans Macrophages / metabolism* Mechanistic Target of Rapamycin Complex 1 / genetics Mechanistic Target of Rapamycin Complex 1 / metabolism* Mice Mice, Inbred BALB C Mice, Inbred C57BL NF-kappa B / metabolism Proteomics Signal Transduction / genetics Signal Transduction / physiology |
| IF | 7.815 |
| 引用数 | 30 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |