PXD002444

PXD002444 is an original dataset announced via ProteomeXchange.

Title	Proteome and secretome of human mammary normal fibroblasts and CAF
Description	The secretome of cancer and stromal cells generates a microenvironment which contributes to tumour cell invasion and angiogenesis. Here, we compare the secretome of human mammary normal fibroblasts and cancer-associated fibroblasts (CAF). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminse-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase which reduces TGM2 and regulate TGM2 binding to its cofactors. Finally, CLIC3 is secreted also by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers, and its levels correlate with poor clinical outcome. This work reveals an unprecedented invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:06:00.672.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Zanivan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-06-29 05:38:25	ID requested
1	2016-12-13 16:03:05	announced
2	2018-03-08 00:09:53	announced	Updated publication reference for PubMed record(s): 28198360.
⏵ 3	2024-10-22 04:06:08	announced	2024-10-22: Updated project metadata.

Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D, Hoyle A, Kuchnio A, Carmeliet P, Valenzuela SM, Blyth K, Yin H, Mazzone M, Norman JC, Zanivan S, Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun, 8():14206(2017) [pubmed]

10.1038/ncomms14206;

submitter keyword: TGM2,CAF, cysteine oxidation, fibroblasts, CLIC3, LC-MS/MS

Sara Zanivan
contact affiliation	CRUK Beatson Institute
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sara Zanivan
contact affiliation	Tumour Microenvironment & Proteomics
contact email	s.zanivan@beatson.gla.ac.uk
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/2016/12/PXD002444

PRIDE project URI

• PRIDE
  1. PXD002444
     1. Label: PRIDE project
     2. Name: Proteome and secretome of human mammary normal fibroblasts and CAF