PXD006396-3

PXD006396 is an original dataset announced via ProteomeXchange.

Title	Proteomics reveals NNMT as a master metabolic regulator of cancer associated fibroblasts
Description	High-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.
HostingRepository	PRIDE
AnnounceDate	2019-04-19
AnnouncementXML	Submission_2019-06-03_01:27:56.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.

Eckert MA, Coscia F, Chryplewicz A, Chang JW, Hernandez KM, Pan S, Tienda SM, Nahotko DA, Li G, Bla, ž, enovi, ć 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]

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: Proteomics reveals NNMT as a master metabolic regulator of cancer associated fibroblasts