title: Repression of NR4A1 by a chromatin modifier promotes docetaxel resistance in PC-3 human prostate cancer cells.
abstract: Epigenetic silencing mechanisms play an important role in chemoresistance of human cancer. Here we report the upregulated expression of metastasis-associated protein 1 (MTA1), a component of the nucleosome remodeling deacetylation (NuRD) complex, in chemoresistant prostate cancer (PCa). MTA1 knockdown in PC-3 cells inhibited cell proliferation and enhanced docetaxel (DTX)-induced cell death. Conversely, overexpression of MTA1 promotes DTX chemoresistance in PC-3 cells. MTA1 acted as a potent corepressor of the nuclear receptor NR4A1 transcription by interacting with histone deacetylase 2 (HDAC2). These findings suggest that MTA1 may serve as a novel DTX-resistance promoter in PC-3 cells.
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Road, Xi'an 710032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Yan-sheng
authors.initials: YS
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D002843:Chromatin / Q000737:chemistry*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008297:Male; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D015534:Trans-Activators; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C089320:MTA1 protein, human; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012097:Repressor Proteins; D043823:Taxoids; D015534:Trans-Activators; D000077143:Docetaxel; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: Chemoresistance; Metastasis-associated protein 1 (MTA1); Nucleosome remodeling deacetylation (NuRD) complex; Prostate cancer (PCa)