PXD039209-1

PXD039209 is an original dataset announced via ProteomeXchange.

Title	Breast cancer identity is determined by glucocorticoid receptor activity status
Description	Glucocorticoid receptor (GR) is a ligand-inducible transcription factor with an intricate role in cancer biology. Using an in silico designed GR activity signature we show that GR is a tumor suppressor across diverse primary cancers. In breast cancer, GR activity status determines luminal identity, and importantly, relates to patients’ outcomes. We illustrate that GR suppresses tumor growth, mediated through its engagement with the estrogen receptor-α (ER). This steroid hormone receptor cross-talk leads to redistribution of ERα on chromatin, ultimately leading to expression of ZBTB16 gene. We define ZBTB16 as a transcriptional repressor and a tumor suppressor in ER-positive breast cancer. Importantly, highly aggressive ER-positive breast cancer cells displaying absence of GR activity can be eradicated if GR-induced gene repression is mimicked by inhibitors of the epigenetic pathway. In line with this, epigenetic regulators are highly expressed upon GR activity loss, leading to vulnerability of aggressive breast cancer cells to clinically available epigenetic inhibitors. Our findings indicate that GR functions as a tumor suppressor by repositioning ER to specific sites on chromatin, modulating targetable pathways, which has important implications for patients’ prognosis and therapeutic interventions.
HostingRepository	PRIDE
AnnounceDate	2023-10-02
AnnouncementXML	Submission_2023-10-02_05:23:08.698.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LiesbethHoekman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-03 00:56:51	ID requested
⏵ 1	2023-10-02 05:23:09	announced

Dataset with its publication pending

submitter keyword: Human, LC-MSMS, breast cancer, Glucocorticoid receptor GR, estrogen receptor-alpha (ER), ZBTB16

MaartenAltelaar
contact affiliation	1 Proteomics Facility, Netherlands Cancer Institute, Amsterdam, Netherlands. 2 Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, Utrecht University and Netherlands Proteomics Centre, Utrecht, The Netherlands.
contact email	m.altelaar@nki.nl
lab head
LiesbethHoekman
contact affiliation	The Netherlands Cancer Institute, Amsterdam, The Netherlands.
contact email	l.hoekman@nki.nl
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/2023/10/PXD039209

PRIDE project URI

• PRIDE
  1. PXD039209
     1. Label: PRIDE project
     2. Name: Breast cancer identity is determined by glucocorticoid receptor activity status