Androgen receptor-mediated transcriptional repression targets cell plasticity in prostate cancer.

Autor: Erdmann É; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France., Ould Madi Berthélémy P; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France., Cottard F; University of Freiburg, Freiburg im Breisgau, Germany., Angel CZ; Genomic Medicine Research Group, BMSRI, Ulster University, Belfast, UK., Schreyer E; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France., Ye T; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France., Morlet B; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France., Negroni L; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France., Kieffer B; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France., Céraline J; CNRS UMR 7104, INSERM U1258, IGBMC, University de Strasbourg, Illkirch, France.; Institut de Cancérologie de Strasbourg Europe (ICANS), Hôpitaux Universitaires de Strasbourg, Strasbourg, France.; Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg, FMTS, Université de Strasbourg, Illkirch, France.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2022 Jul; Vol. 16 (13), pp. 2518-2536. Date of Electronic Publication: 2022 Feb 02.
DOI: 10.1002/1878-0261.13164
Abstrakt: Androgen receptor (AR) signaling remains the key therapeutic target in the management of hormone-naïve-advanced prostate cancer (PCa) and castration-resistant PCa (CRPC). Recently, landmark molecular features have been reported for CRPC, including the expression of constitutively active AR variants that lack the ligand-binding domain. Besides their role in CRPC, AR variants lead to the expression of genes involved in tumor progression. However, little is known about the specificity of their mode of action compared with that of wild-type AR (AR-WT). We performed AR transcriptome analyses in an androgen-dependent PCa cell line as well as cross-analyses with publicly available RNA-seq datasets and established that transcriptional repression capacity that was marked for AR-WT was pathologically lost by AR variants. Functional enrichment analyses allowed us to associate AR-WT repressive function to a panel of genes involved in cell adhesion and epithelial-to-mesenchymal transition. So, we postulate that a less documented AR-WT normal function in prostate epithelial cells could be the repression of a panel of genes linked to cell plasticity and that this repressive function could be pathologically abrogated by AR variants in PCa.
(© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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