PXD058744

PXD058744 is an original dataset announced via ProteomeXchange.

Title	GATAD2B O-GlcNAcylation regulates breast cancer stem-like potential and drug resistance
Description	The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically decreases mammosphere formation efficiency, CSCs population and expression of CSCs factors. O-GlcNAcylation of GATAD2B at the C-terminus protects GATAD2B from ubiquitination and proteasomal degradation in breast cancer cells. We identify ITCH as a novel E3 ligase for GATAD2B and show that targeting ITCH genetically increases GATAD2B levels and increases CSCs phenotypes in breast cancer cells. Lastly, we show that overexpression of wild-type GATAD2B, but not the mutant lacking C-terminal O-GlcNAc sites, promotes mammosphere formation, expression of CSCs factors and drug resistance. Together, we identify a critical role of GATAD2B and ITCH in regulating CSCs in breast cancer and GATAD2B O-GlcNAcylation as a mechanism regulating breast cancer stem-like populations and promoting chemoresistance.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_05:56:32.484.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	O-(N-acetylamino)glucosyl-L-threonine; phosphorylated residue; O-(N-acetylamino)glucosyl-L-serine
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-10 14:06:54	ID requested
⏵ 1	2025-05-07 05:56:33	announced

10.3390/cells14060398;

Le Minh G, Merzy J, Esquea EM, Ahmed NN, Young RG, Sharp RJ, Dhameliya TT, Agana B, Lee MH, Bethard JR, Comte-Walters S, Ball LE, Reginato MJ, GATAD2B O-GlcNAcylation Regulates Breast Cancer Stem-like Potential and Drug Resistance. Cells, 14(6):(2025) [pubmed]

submitter keyword: cancer stem cell, cancer, NuRD, GATAD2B,: OGT, O-GlcNAc, signaling, chemoresistance

Mauricio J. Reginato
contact affiliation	Department of Biochemistry and Molecular Biology, Drexel University College of Medicine. Translational Cellular Oncology Program, Sidney Kimmel Cancer Center, Thomas Jefferson University
contact email	mjr53@drexel.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.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/2025/05/PXD058744

PRIDE project URI

• PRIDE
  1. PXD058744
     1. Label: PRIDE project
     2. Name: GATAD2B O-GlcNAcylation regulates breast cancer stem-like potential and drug resistance