PXD006396-1

PXD006396 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: Ovarian Cancer Proteomics Laser Microdissection

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD006396

PRIDE project URI

• PRIDE
  1. PXD006396
     1. Label: PRIDE project
     2. Name: Compartment-resolved proteomics reveals NNMT as a master metabolic regulator of cancer associated fibroblasts