{"doi":"10.3390/cells12162046","title":"Glucocorticoid Receptor Regulates and Interacts with LEDGF/p75 to Promote Docetaxel Resistance in Prostate Cancer Cells","abstract":"Patients with advanced prostate cancer (PCa) invariably develop resistance to anti-androgen therapy and taxane-based chemotherapy. Glucocorticoid receptor (GR) has been implicated in PCa therapy resistance; however, the mechanisms underlying GR-mediated chemoresistance remain unclear. Lens epithelium-derived growth factor p75 (LEDGF/p75, also known as PSIP1 and DFS70) is a glucocorticoid-induced transcription co-activator implicated in cancer chemoresistance. We investigated the contribution of the GR-LEDGF/p75 axis to docetaxel (DTX)-resistance in PCa cells. GR silencing in DTX-sensitive and -resistant PCa cells decreased LEDGF/p75 expression, and GR upregulation in enzalutamide-resistant cells correlated with increased LEDGF/p75 expression. ChIP-sequencing revealed GR binding sites in the LEDGF/p75 promoter. STRING protein-protein interaction analysis indicated that GR and LEDGF/p75 belong to the same transcriptional network, and immunochemical studies demonstrated their co-immunoprecipitation and co-localization in DTX-resistant cells. The GR modulators exicorilant and relacorilant increased the sensitivity of chemoresistant PCa cells to DTX-induced cell death, and this effect was more pronounced upon LEDGF/p75 silencing. RNA-sequencing of DTX-resistant cells with GR or LEDGF/p75 knockdown revealed a transcriptomic overlap targeting signaling pathways associated with cell survival and proliferation, cancer, and therapy resistance. These studies implicate the GR-LEDGF/p75 axis in PCa therapy resistance and provide a pre-clinical rationale for developing novel therapeutic strategies for advanced PCa.","journal":"Cells","year":2023,"id":349930,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1093882,"name":"Pedro T. Ochoa","orcid":null,"position":1,"is_corresponding":false},{"id":1093486,"name":"Tise Suzuki","orcid":"0000-0003-2049-1612","position":2,"is_corresponding":false},{"id":329103,"name":"Greisha L. Ortiz-Hernández","orcid":"0000-0001-9271-9458","position":3,"is_corresponding":false},{"id":930824,"name":"Juli Unternaehrer","orcid":"0000-0001-5864-4704","position":4,"is_corresponding":false},{"id":925207,"name":"Hossam R. Alkashgari","orcid":null,"position":5,"is_corresponding":false},{"id":1093883,"name":"Carlos J. Díaz Osterman","orcid":null,"position":6,"is_corresponding":false},{"id":924743,"name":"Shannalee R. Martinez","orcid":"0000-0002-9682-0227","position":7,"is_corresponding":false},{"id":559579,"name":"Zhong Chen","orcid":"0000-0003-2444-8216","position":8,"is_corresponding":false},{"id":295692,"name":"Isaac Kremsky","orcid":"0000-0003-1160-1373","position":9,"is_corresponding":false},{"id":24562,"name":"Charles Wang","orcid":null,"position":10,"is_corresponding":false},{"id":329104,"name":"Carlos A. Casiano","orcid":"0000-0002-7320-4333","position":11,"is_corresponding":false},{"id":330308,"name":"Evelyn S. Sanchez-Hernández","orcid":null,"position":0,"is_corresponding":true}],"reference_count":126,"raw_metadata":null,"created_at":"2026-07-19T01:12:19.059218Z","pmid":"37626856","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":[]}