ArticleCancers2021
p38 MAPK Inhibition Mitigates Hypoxia-Induced AR Signaling in Castration-Resistant Prostate Cancer.
Article in Cancers, 2021. 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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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Phenoxazine Derivative ST61 Displays an Oxidative-Stress-Mediated Cytotoxic Activity Against Human Cancer Cells.Biomolecules · 2026Article
- Review
- Induction of cellular senescence by androgen receptor agonist or antagonist is mediated via two novel common DYRK1A-DREAM and cyclin G2 signaling pathways in castration-resistant prostate cancer.Journal of advanced research · 2026Article
- Magnocurarine inhibits migration and invasion by suppressing mesenchymal marker expression and MAPK signaling in castration-resistant prostate cancer cells.Frontiers in pharmacology · 2026Article
- Exploring the pharmacological mechanisms of resibufogenin in castration-resistant prostate cancer via network pharmacology and experimental validation.Frontiers in oncology · 2026Article
- Unraveling the Carcinogenic Mechanisms of Food Contaminants: An Integrated in Silico Framework Combining Network Toxicology, Machine Learning, and Molecular Docking.Journal of food science · 2025Article
- Discoidin Domain Receptor 2 (DDR2) Promotes Prostate Cancer Progression in Cooperation with Collagen Remodeling.Acta histochemica et cytochemica · 2025Article
- Comparative Analysis of miRNA Expression 106a-5p and 375-3p and Proteins ERK1/2, p38, β-Catenin and E-Cadherin in Prostate Cancer and Benign Prostatic Hyperplasia.Journal of cellular and molecular medicine · 2025Article
- Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).International journal of oncology · 2023Review
- SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway.Cancer medicine · 2023Article
- Theranostic applications of selenium nanomedicines against lung cancer.Journal of nanobiotechnology · 2023Review
- Identification of a novel senescence-associated signature to predict biochemical recurrence and immune microenvironment for prostate cancer.Frontiers in immunology · 2023Article
- Androgen-Responsive Oncogenic lncRNA RP11-1023L17.1 Enhances c-Myc Protein Stability in Prostate Cancer.International journal of molecular sciences · 2022Article
- Review
- Review
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
- Gene Differential Expression and Interaction Networks Illustrate the Biomarkers and Molecular Mechanisms of Atherosclerotic Cerebral Infarction.Journal of healthcare engineering · 2022Article
- Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade.International journal of biological sciences · 2022Article
- The Hypoxia-Long Noncoding RNA Interaction in Solid Cancers.International journal of molecular sciences · 2021Review
- Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity.Asian journal of andrologyArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundAberrant androgen receptor (AR) signaling is a major driver of castration-resistant prostate cancer (CRPC). Tumor hypoxia increases AR signaling and is associated with treatment resistance in prostate cancer. Heat shock protein 27 (Hsp27) is a molecular chaperone that is activated in response to heat shock and hypoxia. Hsp27 has previously been reported to facilitate AR nuclear translocation in a p38 mitogen-activated protein kinase (MAPK) dependent manner in castration-sensitive prostate cancer cell lines. Here, we evaluated the potential for inhibiting p38 MAPK/Hsp27 mediated AR signaling under normoxia and hypoxia in experimental models of CRPC.
methodsWe inhibited p38 MAPK with SB203580 in prostate cancer cell lines and measured Hsp27 phosphorylation, AR activity, cell proliferation, and clonogenicity under normoxia and hypoxia. AR activity was measured using an androgen response element driven reporter assay and qPCR to measure expression of AR target genes. Xenograft-bearing mice were treated with SB203580 to measure tumor growth and serum prostate specific antigen (PSA).
resultsOur results indicate that p38 MAPK and Hsp27 are activated under normoxia and hypoxia in response to androgens in CRPC cells. p38 MAPK inhibition diminished Hsp27 activation and the hypoxia-mediated increase in AR activity. Additionally, inhibition of p38 MAPK activity decreased proliferation and survival of CRPC cells in vitro and prolonged the survival of tumor-bearing mice.
conclusionsThese results suggest that p38 MAPK inhibition may represent a therapeutic strategy to disrupt AR signaling in the heterogeneous CRPC tumor microenvironment.
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