Androgen receptor-mediated transcriptional repression targets cell plasticity in prostate cancer.
Fiche publication
Date publication
décembre 2021
Journal
Molecular oncology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CERALINE Jocelyn, Dr KIEFFER Bruno, Dr NEGRONI Luc, Mr MORLET Bastien, Dr COTTARD Félicie
Tous les auteurs :
Erdmann É, Ould Madi Berthélémy P, Cottard F, Angel CZ, Schreyer E, Ye T, Morlet B, Negroni L, Kieffer B, Céraline J
Lien Pubmed
Résumé
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.
Mots clés
AR-V7, Androgen receptor, Cell plasticity, EMT, Prostate cancer, Transcriptional repression
Référence
Mol Oncol. 2021 Dec 17;: