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PXD006396

PXD006396 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomics reveals NNMT as a master metabolic regulator of cancer associated fibroblasts
DescriptionHigh-grade serous carcinoma has a poor prognosis, owing primarily to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer, but a systematic examination of both the tumour and stromal compartments is critical in understanding ovarian cancer metastasis. We developed a label- free proteomic workflow to analyse as few as 5,000 formalin-fixed, paraffin-embedded cells microdissected from each compartment. The tumour proteome was stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and several of the proteins that it regulates. Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT expression supported ovarian cancer migration, proliferation and in vivo growth and metastasis. Expression of NNMT in CAFs led to depletion of S-adenosyl methionine and reduction in histone methylation associated with widespread gene- expression changes in the tumour stroma. This work supports the use of ultra-low-input proteomics to identify candidate drivers of disease phenotypes. NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma that may be therapeutically targeted.
HostingRepositoryPRIDE
AnnounceDate2019-04-19
AnnouncementXMLSubmission_2019-06-03_01:27:56.xml
DigitalObjectIdentifier
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
Eckert MA, Coscia F, Chryplewicz A, Chang JW, Hernandez KM, Pan S, Tienda SM, Nahotko DA, Li G, Blaženović I, Lastra RR, Curtis M, Yamada SD, Perets R, McGregor SM, Andrade J, Fiehn O, Moellering RE, Mann M, Lengyel E, Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature, 569(7758):723-728(2019) [pubmed]
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
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Dataset FTP location
PRIDE project URI
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