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PXD006396 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCompartment-resolved proteomics reveals NNMT as a master metabolic regulator of cancer associated fibroblasts
DescriptionThe lethality of high grade serous carcinoma (HGSC) is primarily due to its early dissemination throughout the abdominal cavity. Recent genomic and proteomic approaches provide snapshots of molecular alterations that have occurred in ovarian cancer (OvCa), but have not systematically examined the protein changes in both the tumor and stroma compartments during the progression from in situ lesions to metastatic disease. We developed a label-free proteomic workflow to analyze as few as 5,000 microdissected cells from each compartment and identified a highly conserved molecular signature of stromal proteins associated with metastasis, which prominently included nicotinamide N-methyltransferase (NNMT). Functionally, stromal NNMT expression was found to be necessary and sufficient for multiple aspects of the cancer associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix support OvCa migration, proliferation, and in vivo growth and metastasis. High expression of NNMT in CAFs led to a depletion of S-adenosyl methionine (SAM) and a reduction in histone methylation associated with gene expression changes in the tumor stroma. This work supports the use of ultra-low input proteomics to identify candidate drivers of disease phenotypes and reveals that NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMario Oroshi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-04-27 01:47:27ID requested
12019-04-18 09:35:31announced
22019-04-19 00:30:33announcedUpdated project metadata.
32019-06-03 01:27:57announcedUpdated project metadata.
Publication List
Dataset with its publication pending
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: Ovarian Cancer Proteomics Laser Microdissection
Contact List
Matthias Mann
contact affiliationMax Planck Institute of Biochemistry Department of Proteomics and Signaltransduction Am Klopferspitz 18 D-82152 Martinsried
contact emailmmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliationProteomics
contact emailoroshi@biochem.mpg.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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