ArticleThe Journal of clinical investigation2021
Regulation and targeting of androgen receptor nuclear localization in castration-resistant prostate cancer.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.bioRxiv : the preprint server for biology · 2026Article
- LINC00222 regulates FOXO3 to interfere with β-catenin signaling pathway and suppresses prostate cancer progression.Scientific reports · 2026Article
- Emerging role of HIC1 in prostate cancer progression and therapeutic response: A novel perspective.Journal of cell communication and signaling · 2025Article
- Histone methyltransferase KMT2D targets the SPOP-G3BP1 axis to enhance AR stability and drive castration-resistant prostate cancer progression.Molecular biomedicine · 2025Article
- Unravelling the multifaceted actions of neurosteroids: Machine learning and in vitro screening for novel target discovery.British journal of pharmacology · 2025Article
- Molecular stratification of prostate cancer through sensory perception-related multi-omics analysis reveals chemoresistant mechanisms.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Androgen receptor inhibitors in treating prostate cancer.Asian journal of andrology · 2025Review
- A potent new-scaffold androgen receptor antagonist discovered on the basis of a MIEC-SVM model.Acta pharmacologica Sinica · 2024Article
- UBX-390: A Novel Androgen Receptor Degrader for Therapeutic Intervention in Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Androgen receptor and estrogen receptor variants in prostate and breast cancers.The Journal of steroid biochemistry and molecular biology · 2024Review
- Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation.Nature communications · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).International journal of oncology · 2023Review
- B-type Plexins promote the GTPase activity of Ran to affect androgen receptor nuclear translocation in prostate cancer.Cancer gene therapy · 2023Article
- Androgen receptor nucleocytoplasmic trafficking - A one-way journey.Molecular and cellular endocrinology · 2023Review
- Characterization of allosteric modulators that disrupt androgen receptor co-activator protein-protein interactions to alter transactivation-Drug leads for metastatic castration resistant prostate cancer.SLAS discovery : advancing life sciences R & D · 2023Article
- AR activates YAP/TAZ differentially in prostate cancer.Life science alliance · 2023Article
- Review
- Selective nuclear export inhibitor KPT‑330 enhances the radiosensitivity of esophageal carcinoma cells.Experimental and therapeutic medicine · 2023Article
- Lycopene inhibits endothelial-to-mesenchymal transition of choroidal vascular endothelial cells in laser-induced mouse choroidal neovascularization.Journal of cellular and molecular medicine · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Nuclear localization of the androgen receptor (AR) is necessary for its activation as a transcription factor. Defining the mechanisms regulating AR nuclear localization in androgen-sensitive cells and how these mechanisms are dysregulated in castration-resistant prostate cancer (CRPC) cells is fundamentally important and clinically relevant. According to the classical model of AR intracellular trafficking, androgens induce AR nuclear import and androgen withdrawal causes AR nuclear export. The present study has led to an updated model that AR could be imported in the absence of androgens, ubiquitinated, and degraded in the nucleus. Androgen withdrawal caused nuclear AR degradation, but not export. In comparison with their parental androgen-sensitive LNCaP prostate cancer cells, castration-resistant C4-2 cells exhibited reduced nuclear AR polyubiquitination and increased nuclear AR level. We previously identified 3-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (CPPI) in a high-throughput screen for its inhibition of androgen-independent AR nuclear localization in CRPC cells. The current study shows that CPPI is a competitive AR antagonist capable of enhancing AR interaction with its E3 ligase MDM2 and degradation of AR in the nuclei of CRPC cells. Also, CPPI blocked androgen-independent AR nuclear import. Overall, these findings suggest the feasibility of targeting androgen-independent AR nuclear import and stabilization, two necessary steps leading to AR nuclear localization and activation in CRPC cells, with small molecule inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.