PXD007996 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Noncanonical pathway for regulation of CCL2 expression by an mTORC1-FOXK1 axis promotes recruitment of tumor-associated macrophages |
Description | 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. Mammalian target of rapamycin complex 1 (mTORC1) is a protein kinase that is activated in various tumor cell types. We have now identified a noncanonical pathway for regulation of CCL2 production that is mediated by mTORC1 but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1, with dephosphorylation of FOXK1 in response to mTORC1 activation 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. Specific inhibition of FOXK1 may thus be a potential therapeutic strategy for cancer. |
HostingRepository | PRIDE |
AnnounceDate | 2017-11-30 |
AnnouncementXML | Submission_2017-11-30_01:01:11.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hirokazu Nakatsumi |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iTRAQ4plex-116 reporter+balance reagent acylated residue; phosphorylated residue |
Instrument | QSTAR |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-10-18 07:37:59 | ID requested | |
⏵ 1 | 2017-11-30 01:01:11 | announced | |
2 | 2019-03-07 05:41:07 | announced | Updated publication reference for PubMed record(s): 29186685. |
3 | 2024-10-22 04:16:24 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: HeLa LC-MS/MS |
Contact List
Keiichi I. Nakayama |
contact affiliation | Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Japan |
contact email | nakayak1@bioreg.kyushu-u.ac.jp |
lab head | |
Hirokazu Nakatsumi |
contact affiliation | Kyushu University |
contact email | nakatsumi@bioreg.kyushu-u.ac.jp |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD007996
- Label: PRIDE project
- Name: Noncanonical pathway for regulation of CCL2 expression by an mTORC1-FOXK1 axis promotes recruitment of tumor-associated macrophages