ArticleMolecular cancer therapeutics2015
NF-κB2/p52:c-Myc:hnRNPA1 Pathway Regulates Expression of Androgen Receptor Splice Variants and Enzalutamide Sensitivity in Prostate Cancer.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Review
- Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A.The EMBO journal · 2025Article
- Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 (IGF2BP2) Promotes Castration-Resistant Prostate Cancer Progression by Regulating AR-V7 mRNA Stability.Cancer reports (Hoboken, N.J.) · 2025Article
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Inhibition of Galectin-1 and Androgen Receptor Axis Enhances Enzalutamide Treatment in Enzalutamide Resistant Prostate Cancer.Cancers · 2025Article
- Higher isoform of hnRNPA1 confer Temozolomide resistance in U87MG & LN229 glioma cells.Journal of neuro-oncology · 2025Article
- Enhanced identification of small molecules binding to hnRNPA1 via cryptic pockets mapping coupled with X-Ray fragment screening.bioRxiv : the preprint server for biology · 2024Article
- LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.Cancer research · 2024Article
- Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.Expert review of anticancer therapy · 2024Review
- Computational drug discovery pipelines identify NAMPT as a therapeutic target in neuroendocrine prostate cancer.Clinical and translational science · 2024Article
- Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development.Biomedicines · 2023Review
- Therapeutic Targeting of RNA Splicing in Cancer.Genes · 2023Review
- How Driver Oncogenes Shape and Are Shaped by Alternative Splicing Mechanisms in Tumors.Cancers · 2023Review
- Role of Heterogeneous Nuclear Ribonucleoproteins in the Cancer-Immune Landscape.International journal of molecular sciences · 2023Review
- A comprehensive understanding of hnRNP A1 role in cancer: new perspectives on binding with noncoding RNA.Cancer gene therapy · 2023Review
- Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors.Life (Basel, Switzerland) · 2023Review
- Role of Metabolism and Metabolic Pathways in Prostate Cancer.Metabolites · 2023Review
- JAG1 Intracellular Domain Enhances AR Expression and Signaling and Promotes Stem-like Properties in Prostate Cancer Cells.Cancers · 2022Article
- The Crucial Role of AR-V7 in Enzalutamide-Resistance of Castration-Resistant Prostate Cancer.Cancers · 2022Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Castration-resistant prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling. Alternative splicing of the AR to generate constitutively active, ligand-independent variants is one of the principal mechanisms that promote the development of resistance to next-generation antiandrogens such as enzalutamide. Here, we demonstrate that the splicing factor heterogeneous nuclear RNA-binding protein A1 (hnRNPA1) plays a pivotal role in the generation of AR splice variants such as AR-V7. hnRNPA1 is overexpressed in prostate tumors compared with benign prostates, and its expression is regulated by NF-κB2/p52 and c-Myc. CRPC cells resistant to enzalutamide exhibit higher levels of NF-κB2/p52, c-Myc, hnRNPA1, and AR-V7. Levels of hnRNPA1 and AR-V7 are positively correlated with each other in prostate cancer. The regulatory circuit involving NF-κB2/p52, c-Myc, and hnRNPA1 plays a central role in the generation of AR splice variants. Downregulation of hnRNPA1 and consequently of AR-V7 resensitizes enzalutamide-resistant cells to enzalutamide, indicating that enhanced expression of hnRNPA1 may confer resistance to AR-targeted therapies by promoting the generation of splice variants. These findings may provide a rationale for cotargeting these pathways to achieve better efficacy through AR blockade.
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