ArticlePloS one2013
The role of hypoxia-inducible factor 1α in determining the properties of castrate-resistant prostate cancers.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 74 citations in OpenAlex.
- Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial.Journal of translational medicine · 2016Trial
- Metabolic Modulation by Dimethyl Fumarate Alters Docetaxel Responses in Prostate Cancer Cells.International journal of molecular sciences · 2026Article
- Alpha-Lipoic Acid Inhibits IFN-γ-Induced PD-L1 Expression in Prostate Cancer Cells and Enhances T-Cell-Mediated Anti-Tumor Cytotoxicity.Antioxidants (Basel, Switzerland) · 2026Article
- Microwell-based flow culture increases viability and restores drug response in prostate cancer spheroids.Biotechnology journal · 2023Article
- Evaluation of the Cytotoxic Effect of PdInternational journal of molecular sciences · 2023Article
- A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer.Frontiers in oncology · 2023Review
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- Immunofluorescence-Based Method to Assess Cancer Biomarker in the Hypoxic Region of the Tumor.Methods in molecular biology (Clifton, N.J.) · 2022Article
- p38 MAPK Inhibition Mitigates Hypoxia-Induced AR Signaling in Castration-Resistant Prostate Cancer.Cancers · 2021Article
- Identification of a Hypoxia-Related Gene Signature for Predicting Systemic Metastasis in Prostate Cancer.Frontiers in cell and developmental biology · 2021Article
- Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis.Frontiers in molecular biosciences · 2021Article
- Mechanisms of Taxane ResistanceCancers · 2020Review
- Serum zinc level and tissue ZIP4 expression are related to the prognosis of patients with stages I-III colon cancer.Translational cancer research · 2020Article
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- Copper and zinc levels in plasma and cancerous tissues and their relation with expression of VEGF and HIF-1 in the pathogenesis of muscle invasive urothelial bladder cancer: a case-controlled clinical study.Environmental science and pollution research international · 2020Article
- Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre-metastatic niches.Molecular carcinogenesis · 2020Article
- Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells by Enhancing RACK1-Mediated Degradation of HIF-1Oxidative medicine and cellular longevity · 2020Article
- C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer?Pathology oncology research : POR · 2019Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCastrate-resistant prostate cancer (CRPC) is a lethal condition in patients receiving androgen deprivation therapy for prostate cancer (PC). Despite numerous studies showing the expression of HIF1α protein under normoxia in PC cell lines, the role of this normoxic HIF1α expression in chemo-resistance and migration has not been investigated previously. As no method is currently available to determine which tumors will progress to CRPC, the role of HIF1α in PC and its potential for predicting the development of CRPC was also investigated.
methodsThe effect of HIF1α protein knockdown on chemo-resistance and migration of PC3 cells was assessed by cell counting and Transwell assays, respectively. Translation efficiency of HIF1α mRNA was determined in PC cells using a HIF1α 5'UTR-luciferase construct. Clinical outcomes were correlated following the staining of 100 prostate tumors for HIF1α expression.
resultsThe CRPC-like cell lines (PC3 and DU145) expressed more HIF1α protein than an androgen sensitive cell line (LNCaP). Migration rate and chemo-resistance were higher in the PC3 cells and both were decreased when HIF1α expression was reduced. Increased translation of HIF1α mRNA may be responsible for HIF1α overexpression in PC3 cells. Patients whose tumors expressed HIF1α had significantly decreased metastasis-free survival and the patients who were on androgen-deprivation therapy had decreased CRPC-free survival on Kaplan-Meier analysis. On multivariate analysis HIF1α was an independent risk factor for progression to metastatic PC (Hazard ratio (HR) 9.8, p = 0.017) and development of CRPC (HR 10.0, p = 0.021) in patients on androgen-deprivation therapy. Notably the tumors which did not express HIF1α did not metastasize or develop CRPC.
conclusionsHIF1α is likely to contribute to metastasis and chemo-resistance of CRPC and targeted reduction of HIF1α may increase the responsiveness of CRPCs to chemotherapy. Expression of HIF1α may be a useful screening tool for development of CRPC.
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