{"doi":"10.3390/cells14060398","title":"GATAD2B O-GlcNAcylation Regulates Breast Cancer Stem-like Potential and Drug Resistance","abstract":"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 impairs mammosphere formation, decreases expression of self-renewal factors and CSCs population. 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. 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 key 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.","journal":"Cells","year":2025,"id":530501,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9426,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1174458,"name":"Jessica Merzy","orcid":null,"position":1,"is_corresponding":false},{"id":1027312,"name":"Emily M. Esquea","orcid":null,"position":2,"is_corresponding":false},{"id":1221091,"name":"Nusaiba N. Ahmed","orcid":null,"position":3,"is_corresponding":false},{"id":1026460,"name":"Riley G. Young","orcid":"0009-0003-5654-8526","position":4,"is_corresponding":false},{"id":1410183,"name":"Ryan L. Sharp","orcid":"0000-0002-5926-2799","position":5,"is_corresponding":false},{"id":1410497,"name":"Tejsi T. Dhameliya","orcid":null,"position":6,"is_corresponding":false},{"id":517434,"name":"Bernice A. Agana","orcid":"0000-0002-8947-6413","position":7,"is_corresponding":false},{"id":927629,"name":"Mi‐Hye Lee","orcid":"0000-0002-5484-3383","position":8,"is_corresponding":false},{"id":371310,"name":"Jennifer R. Bethard","orcid":"0000-0001-7653-156X","position":9,"is_corresponding":false},{"id":707071,"name":"Susana Comte‐Walters","orcid":null,"position":10,"is_corresponding":false},{"id":361356,"name":"Lauren E. Ball","orcid":"0000-0001-6780-1679","position":11,"is_corresponding":false},{"id":344706,"name":"Mauricio J. Reginato","orcid":"0000-0002-7541-4094","position":12,"is_corresponding":false},{"id":916182,"name":"Giang Le Minh","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:05.836974Z","pmid":"40136647","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}