PXD022826-1

PXD022826 is an original dataset announced via ProteomeXchange.

Title	A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in cancer
Description	The remodeling of the extracellular matrix (ECM) by proteases releases fragments that promote tumor progression and metastasis. The protease cathepsin D (cath-D), a marker of poor prognosis in triple-negative breast cancer (TNBC), is aberrantly secreted in the ECM. Using degradomics, we discovered that the matricellular protein SPARC is a substrate of extracellular cath-D. In vitro, cath-D induced limited proteolysis of SPARC C-terminal extracellular Ca2+ binding domain at acidic pH, leading to the production of SPARC fragments (34-, 27-, 16-, 9-, and 6-kDa). Cath-D secreted by TNBC cells cleaved fibroblast- and cancer cell-derived SPARC at the tumor pericellular pH. SPARC cleavage also occurred in TNBC tumors. Among these fragments, the 9-kDa SPARC fragment inhibited TNBC cell adhesion and spreading, and stimulated their migration, endothelial transmigration and invasion more potently than full-length SPARC. Our study establishes a novel crosstalk between proteases and matricellular proteins in the ECM through limited proteolysis of SPARC, revealing a novel targetable 9-kDa bioactive SPARC fragment for TNBC.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_14:27:09.843.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022826
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Frederic DELOLME
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-30 06:46:33	ID requested
⏵ 1	2021-09-09 14:27:10	announced

Alcaraz LB, Mallavialle A, David T, Derocq D, Delolme F, Dieryckx C, Mollevi C, Boissi, è, re-Michot F, Simony-Lafontaine J, Du Manoir S, Huesgen PF, Overall CM, Tartare-Deckert S, Jacot W, Chard, è, s T, Guiu S, Roger P, Reinheckel T, Moali C, Liaudet-Coopman E, A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in the triple-negative breast cancer microenvironment. Theranostics, 11(13):6173-6192(2021) [pubmed]

submitter keyword: matricellular protein, protease, proteolysis, tumor microenvironment, ECM, TNBC

Emmanuelle LIAUDET-COOPMAN
contact affiliation	Montpellier Cancer Research Institute lab : Protease, Microenvironment and Cancer
contact email	emmanuelle.liaudet-coopman@inserm.fr
lab head
Frederic DELOLME
contact affiliation	CNRS UMS3444 Protein Science Facility
contact email	frederic.delolme@ibcp.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022826
     1. Label: PRIDE project
     2. Name: A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in cancer