PXD067936

PXD067936 is an original dataset announced via ProteomeXchange.

Title	GYLATL1 promotes endocrine therapy resistance in luminal A-like breast cancer and is regulated by estrogen-independent ERα signaling
Description	Luminal A breast cancer is characterized by the expression and activity of estrogen receptor-α (ERα), a biomarker and therapeutic target. While endocrine therapies targeting ER signaling have shown efficacy, long-term success is limited by the development of resistance. Almost 40% of ER-positive breast cancer patients presenting with late-stage disease either fail to respond to endocrine therapies or relapse due to acquired resistance, leading to poor prognosis. Here, we focused on aromatase inhibition, which is administered to patients in menopause, and found strong upregulation of GLYATL1 (glutamine-N-acyltransferase) in two endocrine therapy-resistant in vitro models. Increased expression of GLYATL1 was found also in patients during treatment and its expression was significantly correlated with poor survival in luminal A breast cancer patients after administration of aromatase inhibitors. Interference with GLYATL1 reversed the resistance phenotype in both in vitro models. GLYATL1 expression was associated with overall decreased TCA cycle activity, however, accumulation of succinate, and with altered histone modifications. Unexpectedly, GLYATL1 expression was found to be positively regulated by estrogen-receptor, yet only in estrogen-deprived conditions suggesting that GLYATL1 is a novel factor in endocrine therapy-resistance of luminal breast cancer, impinging on metabolism and epigenetic gene regulation.
HostingRepository	PRIDE
AnnounceDate	2026-01-30
AnnouncementXML	Submission_2026-01-30_03:59:06.904.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luisa Schwarzmüller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-01 02:01:59	ID requested
⏵ 1	2026-01-30 03:59:07	announced

Dataset with its publication pending

submitter keyword: breast cancer, PRM, GLYATL1, endocrine therapy resistance,DIA

Prof. Dr. Stefan Wiemann
contact affiliation	Molecular Genome Analysis Deutsches Krebsforschungszentrum (DKFZ) Im Neuenheimer Feld 280 69120 Heidelberg Germany
contact email	s.wiemann@dkfz.de
lab head
Luisa Schwarzmüller
contact affiliation	German Cancer Research Center (DKFZ)
contact email	luisa.schwarzmueller@dkfz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067936
     1. Label: PRIDE project
     2. Name: GYLATL1 promotes endocrine therapy resistance in luminal A-like breast cancer and is regulated by estrogen-independent ERα signaling