PXD037543

PXD037543 is an original dataset announced via ProteomeXchange.

Title	Matrix Gla Protein acts as a driver of stemness and tumor initiation in ovarian cancer
Description	Ovarian cancer (OC) displays the highest mortality among gynecological tumors, mainly due to early peritoneal dissemination, the high frequency of tumor relapse following primary debulking and the development of chemoresistance. All these events are thought to be initiated and sustained by a subpopulation of neoplastic cells, termed ovarian cancer stem cells (OCSC), that are endowed with self-renewing and tumor-initiating properties. This implies that interfering with OCSC function should offer novel therapeutic perspectives to defeat OC progression. To this aim, a better understanding of the molecular and functional makeup of OCSC in clinically relevant model systems is essential. We have profiled the transcriptome of OCSC vs. their bulk cell counterpart from a panel of patient-derived OC cell cultures. This revealed that Matrix Gla Protein (MGP), classically known as a calcification-preventing factor in cartilage and blood vessels, is markedly enriched in OCSC. Functional assays showed that MGP confers several stemness-associated traits to OC cells, including a transcriptional reprogramming. Patient-derived organotypic cultures pointed to the peritoneal microenvironment as a major inducer of MGP expression in OC cells. Furthermore, MGP was found to be necessary and sufficient for tumor initiation in OC mouse models, by shortening tumor latency and increasing dramatically the frequency of tumor-initiating cells. Mechanistically, MGP-driven OC stemness was mediated by the stimulation of Hedgehog signaling, in particular through the induction of the Hedgehog effector GLI1, thus highlighting a novel MGP/Hedgehog pathway axis in OCSC. Finally, MGP expression was found to correlate with poor prognosis in OC patients, and was increased in tumor tissue after chemotherapy, supporting the clinical relevance of our findings. Thus, MGP is a novel driver in OCSC pathophysiology, with a major role in stemness and in tumor initiation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:48.850.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Giulia Franciosa
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-19 02:37:38	ID requested
1	2023-05-10 15:04:54	announced
⏵ 2	2023-11-14 08:47:56	announced	2023-11-14: Updated project metadata.

Nieddu V, Melocchi V, Battistini C, Franciosa G, Lupia M, Stellato C, Bertalot G, Olsen JV, Colombo N, Bianchi F, Cavallaro U, Matrix Gla Protein drives stemness and tumor initiation in ovarian cancer. Cell Death Dis, 14(3):220(2023) [pubmed]

submitter keyword: Exploris 480

Matrix Gla protein

Ovarian cancer

Cancer stem cells

Tumor initiation

Hedgehog pathway

Jesper Velgaard Olsen
contact affiliation	University of Copenhagen Faculty of Health and Medical Sciences Novo Nordisk Foundation Center for Protein Research Proteomics Program Blegdamsvej 3B, DK-2200 Copenhagen N Denmark
contact email	jesper.olsen@cpr.ku.dk
lab head
Giulia Franciosa
contact affiliation	Novo Nordisk Foundation Center For Protein Research, Copenhagen University, Copenhagen
contact email	giulia.franciosa@cpr.ku.dk
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/2023/05/PXD037543

PRIDE project URI

• PRIDE
  1. PXD037543
     1. Label: PRIDE project
     2. Name: Matrix Gla Protein acts as a driver of stemness and tumor initiation in ovarian cancer