PXD006396 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Compartment-resolved proteomics reveals NNMT as a master metabolic regulator of cancer associated fibroblasts |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2019-04-18 |
AnnouncementXML | Submission_2019-04-18_09:35:30.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mario Oroshi |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-04-27 01:47:27 | ID requested | |
⏵ 1 | 2019-04-18 09:35:31 | announced | |
2 | 2019-04-19 00:30:33 | announced | Updated project metadata. |
3 | 2019-06-03 01:27:57 | announced | Updated project metadata. |
4 | 2024-10-22 04:37:03 | announced | 2024-10-22: Updated 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 affiliation | Max Planck Institute of Biochemistry Department of Proteomics and Signaltransduction Am Klopferspitz 18 D-82152 Martinsried |
contact email | mmann@biochem.mpg.de |
lab head | |
Mario Oroshi |
contact affiliation | Proteomics |
contact email | oroshi@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD006396
- Label: PRIDE project
- Name: Compartment-resolved proteomics reveals NNMT as a master metabolic regulator of cancer associated fibroblasts