PXD010611

PXD010611 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of human prostate cancer-associated fibroblasts identifies LOXL2 promotes tumour migration in the extracellular matrix
Description	In prostate cancer (PC), cancer-associated fibroblasts (CAFs) exhibit contrasting biological properties to non-malignant prostate fibroblasts (NPFs) and promote tumorigenesis. Resolving intercellular signaling pathways between CAFs and prostate tumor epithelium may offer novel opportunities for research translation. To this end, the proteome and phosphoproteome of four pairs of patient-matched CAFs and NPFs were characterized to identify discriminating proteomic signatures. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a hyper-reaction monitoring data-independent acquisition (HRM-DIA) workflow. Proteins that exhibited a significant increase in CAFs versus NPFs were enriched for the functional categories ‘cell adhesion’ and the ‘extracellular matrix’. The CAF phosphoproteome exhibited enhanced phosphorylation of proteins associated with the ‘spliceosome’ and ‘actin binding’. STRING analysis of the CAF proteome revealed a prominent interaction hub associated with collagen synthesis, modification, and signaling. It contained multiple collagens, including the fibrillar types COL1A1/2 and COL5A1; the receptor tyrosine kinase discoidin domain-containing receptor 2 (DDR2), a receptor for fibrillar collagens; and lysyl oxidase-like 2 (LOXL2), which promotes collagen crosslinking. Increased activity and/or expression of LOXL2 and DDR2 in CAFs were confirmed by enzymatic assays and Western blot analyses. Pharmacological inhibition of CAF-derived LOXL2 perturbed extracellular matrix (ECM) organization and decreased cell migration in wound-healing assays. Furthermore, it significantly impaired the motility of co-cultured RWPE2 prostate tumor epithelial cells. These results indicate that CAF-derived LOXL2 is an important mediator of intercellular communication within the PC tumor microenvironment and a potential therapeutic target.
HostingRepository	PRIDE
AnnounceDate	2019-05-24
AnnouncementXML	Submission_2019-05-24_06:23:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Elizabeth Nguyen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-30 02:29:02	ID requested
1	2019-05-01 10:20:57	announced
⏵ 2	2019-05-24 06:23:43	announced	Updated publication reference for PubMed record(s): 31061140.

Nguyen EV, Pereira BA, Lawrence MG, Ma X, Rebello RJ, Chan H, Niranjan B, Wu Y, Ellem S, Guan X, Wu J, Skhinas JN, Cox TR, Risbridger GP, Taylor RA, Lister NL, Daly RJ, Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment. Mol Cell Proteomics, 18(7):1410-1427(2019) [pubmed]

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biomedical

submitter keyword: Prostate cancer, fibroblast, phosphoproteome, loxl2

Roger Daly
contact affiliation	Monash University Molecular Biology and Biochemistry
contact email	roger.daly@monash.edu
lab head
Elizabeth Nguyen
contact affiliation	Monash University
contact email	mimi.nguyen@monash.edu
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/2019/05/PXD010611

PRIDE project URI

• PRIDE
  1. PXD010611
     1. Label: PRIDE project
     2. Name: Proteomic profiling of human prostate cancer-associated fibroblasts identifies LOXL2 promotes tumour migration in the extracellular matrix