ArticleMolecular endocrinology (Baltimore, Md.)2009
HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 117 citations in OpenAlex.
- Targeting the DNHD1‑HDAC6 axis inactivates prostate cancer cell aggressivenessOncology reports · 2026Article
- HDAC6 orchestrates NK cell maturation and antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- Review
- Dual-Targeting Strategy in Cancer Therapy: The Emerging Role of Pyrrolopyrimidine Scaffolds.Chemistry & biodiversity · 2026Review
- Structure-Based Discovery of Hsp90/HDAC6 Dual Inhibitors Targeting Aggressive Prostate Cancer.Journal of medicinal chemistry · 2025Article
- Searching for Novel HDAC6/Hsp90 Dual Inhibitors with Anti-Prostate Cancer Activity: In Silico Screening and In Vitro Evaluation.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer.Pharmaceutics · 2023Review
- Article
- Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.Epigenetics · 2022Review
- The role of protein acetylation in carcinogenesis and targeted drug discovery.Frontiers in endocrinology · 2022Review
- Posttranslational modification and beyond: interplay between histone deacetylase 6 and heat-shock protein 90.Molecular medicine (Cambridge, Mass.) · 2021Review
- The non-canonical mechanism of ER stress-mediated progression of prostate cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Design and synthesis of isothiocyanate-containing hybrid androgen receptor (AR) antagonist to downregulate AR and induce ferroptosis in GSH-Deficient prostate cancer cells.Chemical biology & drug design · 2021Article
- Shifting the paradigm in treating multi-factorial diseases: polypharmacological co-inhibitors of HDAC6.RSC medicinal chemistry · 2021Review
- Article
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- The classical and updated models of androgen receptor nucleocytoplasmic trafficking.American journal of clinical and experimental urology · 2021Review
- Post-translational modifications of Hsp90 and translating the chaperone code.The Journal of biological chemistry · 2020Review
- Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional HDAC6 pathway.Journal of cell science · 2020Article
- KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells.Cancers · 2020Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The development of castration-resistant prostate cancer (PCa) requires that under castration conditions, the androgen receptor (AR) remains active and thus nuclear. Heat shock protein 90 (Hsp90) plays a key role in androgen-induced and -independent nuclear localization and activation of AR. Histone deacetylase 6 (HDAC6) is implicated, but has not been proven, in regulating AR activity via modulating Hsp90 acetylation. Here, we report that knockdown of HDAC6 in C4-2 cells using short hairpin RNA impaired ligand-independent nuclear localization of endogenous AR and inhibited PSA expression and cell growth in the absence or presence of dihydrotestosterone (DHT). The dose-response curve of DHT-stimulated C4-2 colony formation was shifted by shHDAC6 such that approximately 10-fold higher concentration of DHT is required, indicating a requirement for HDAC6 in AR hypersensitivity. HDAC6 knockdown also inhibited C4-2 xenograft tumor establishment in castrated, but not in testes-intact, nude mice. Studies using HDAC6-deficient mouse embryonic fibroblasts cells showed that inhibition of AR nuclear localization by HDAC6 knockdown can be largely alleviated by expressing a deacetylation mimic Hsp90 mutant. Taken together, our studies suggest that HDAC6 regulates AR hypersensitivity and nuclear localization, mainly via modulating HSP90 acetylation. Targeting HDAC6 alone or in combination with other therapeutic approaches is a promising new strategy for prevention and/or treatment of castration-resistant PCa.
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Registered trials
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 OpenQuestion graph.