PXD007996

PXD007996 is an original dataset announced via ProteomeXchange.

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_2019-03-07_05:41:05.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

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.

Nakatsumi H, Matsumoto M, Nakayama KI, Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages. Cell Rep, 21(9):2471-2486(2017) [pubmed]

submitter keyword: HeLa LC-MS/MS

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

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PRIDE project URI

• PRIDE
  1. PXD007996
     1. Label: PRIDE project
     2. Name: Noncanonical pathway for regulation of CCL2 expression by an mTORC1-FOXK1 axis promotes recruitment of tumor-associated macrophages