ArticleNucleic acids research2020
IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Discovery of N8: a novel IKKε inhibitor with potent anticancer activity via cytotoxicity, migration suppression, and autophagy modulation.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- HOMER3 orchestrates SRC-YAP1 activity that promotes tumor cell growth and antagonizes anti-tumor immunotherapy in prostate cancer.Oncogene · 2025Article
- Integrated proteogenomic characterization of localized prostate cancer identifies biological insights and subtype-specific therapeutic strategies.Nature communications · 2025Article
- AI-based prediction of androgen receptor expression and its prognostic significance in prostate cancer.Scientific reports · 2025Article
- AR and YAP crosstalk: impacts on therapeutic strategies in prostate cancer.Frontiers in oncology · 2025Review
- YAP1 Regulates the YAP1/AR/PSA Axis through Autophagy in Castration-Resistant Prostate Cancer and Mediates T-Cell Immune and Inflammatory Cytokine Infiltration.Biomedicines · 2024Article
- Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis.Science advances · 2024Article
- IKBKE regulates renal cell carcinoma progression and sunitinib resistance through the RRM2-AKT pathway.International journal of biological sciences · 2024Article
- AR activates YAP/TAZ differentially in prostate cancer.Life science alliance · 2023Article
- CDC20 Is Regulated by the Histone Methyltransferase, KMT5A, in Castration-Resistant Prostate Cancer.Cancers · 2023Article
- Pharmacological Efficacy of Repurposing Drugs in the Treatment of Prostate Cancer.International journal of molecular sciences · 2023Review
- Emerging Role of YAP and the Hippo Pathway in Prostate Cancer.Biomedicines · 2022Review
- Effect of taurine on the proliferation, apoptosis andTranslational cancer research · 2022Article
- RNF8 up-regulates AR/ARV7 action to contribute to advanced prostate cancer progression.Cell death & disease · 2022Article
- RNA sequencing and integrative analysis reveal pathways and hub genes associated with TGFβ1 stimulation on prostatic stromal cells.Frontiers in genetics · 2022Article
- Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors.Annals of surgical oncology · 2021Article
- CRISPR screening identifies CDK12 as a conservative vulnerability of prostate cancer.Cell death & disease · 2021Article
- Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2021Article
- Review
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC. Significant inhibition of AR regulated gene expression was observed upon siRNA-mediated IKBKE depletion or pharmacological inhibition due to inhibited AR gene expression in multiple cell line models including a LNCaP derivative cell line resistant to the anti-androgen, enzalutamide (LNCaP-EnzR). Phenotypically, this resulted in significant inhibition of proliferation, migration and colony forming ability suggesting that targeting IKBKE could circumvent resistance to AR targeting therapies. Indeed, pharmacological inhibition in the CWR22Rv1 xenograft mouse model reduced tumour size and enhanced survival. Critically, this was validated in patient-derived explants where enzymatic inactivation of IKBKE reduced cell proliferation and AR expression. Mechanistically, we provide evidence that IKBKE regulates AR levels via Hippo pathway inhibition to reduce c-MYC levels at cis-regulatory elements within the AR gene. Thus, IKBKE is a therapeutic target in advanced PC suggesting repurposing of clinically tested IKBKE inhibitors could be beneficial to castrate resistant PC patients.
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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.