ArticleThe Prostate2022
ATF6α promotes prostate cancer progression by enhancing PLA2G4A-mediated arachidonic acid metabolism and protecting tumor cells against ferroptosis.
Article in The Prostate, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Ferroptosis and prostate cancer: A translational path from molecular mechanisms to precision therapy.Genes & diseases · 2026Review
- PLA2G2F suppresses ferroptosis through phospholipid remodeling.Nature structural & molecular biology · 2026Article
- Inhibition of IRE1α kinase increases ferroptosis resistance in triple-negative breast cancer cells.Oncology letters · 2026Article
- Integrated regulation of ferroptosis in prostate cancer covering mechanisms, resistance, and translational opportunities.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Pirin Transcriptionally Regulates PLA2G4A To Inhibit Ferroptosis in Colorectal Cancer via Lipid Profile Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integration of transcriptomic data reveals lipid metabolic heterogeneity and identifies GSTO1 as a therapeutic target in acute myeloid leukemia.Frontiers in immunology · 2026Article
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma.Molecular oncology · 2025Article
- PSMD14/E2F1 Axis-Mediated CENPF Promotes the Metastasis of Triple-Negative Breast Cancer Through Inhibiting Ferroptosis.Cancer science · 2025Article
- Specificity mechanism of Group VIA calcium-independent phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Developments in the connection between epithelial‑mesenchymal transition and endoplasmic reticulum stress (Review).International journal of molecular medicine · 2025Review
- Crosstalk between ferroptosis and endoplasmic reticulum stress: A potential target for ovarian cancer therapy (Review).International journal of molecular medicine · 2025Review
- Targeting ferroptosis in prostate cancer management: molecular mechanisms, multidisciplinary strategies and translational perspectives.Journal of translational medicine · 2025Review
- Abnormal lipid metabolism and atherosclerosis: a new perspective on organelle function regulation and ferroptosis.Frontiers in immunology · 2025Article
- Dietary resveratrol and β-Hydroxy-β-Methylbutyric acid enhance flavor and modulate intramuscular fat in Tibetan sheep: insights from transcriptomics and lipidomics.Frontiers in veterinary science · 2025Article
- GATA6 Suppresses Lung Adenocarcinoma Progression by Activating CFTR to Modulate Arachidonic Acid Metabolism.Combinatorial chemistry & high throughput screening · 2025Article
- Unlocking ferroptosis in prostate cancer - the road to novel therapies and imaging markers.Nature reviews. Urology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite the clinical success of androgen receptor (AR)-targeted therapies, prostate cancer (PCa) inevitably progresses to castration-resistant prostate cancer (CRPC). Transcription factor 6 α (ATF6α), an effector of the unfolded protein response (UPR) that modulates the cellular response to endoplasmic reticulum (ER) stress, has been linked to tumor development, metastasis, and relapse. However, the role of ATF6α in CRPC remains unclear.
methodsThe effect of ATF6α on the CRPC-like phenotype in PCa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carb-Oxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS), 5-Bromo-2-deoxyUridine (BrdU) incorporation analysis, and cell death assay. Mechanistically, bioinformatic analysis was utilized to evaluate the potential of PLA2G4A as the target of ATF6α. Moreover, Western blot analysis, real-time polymerase chain reaction, chromatin immunoprecipitation, arachidonic acid (AA), and prostaglandin E2 (PGE2) assays were performed to identify the regulatory effect of ATF6α on PLA2G4A.
resultsIn this study, we found that the increase of ATF6α expression in response to androgen deprivation generates PCa cells with a CRPC-like phenotype. PCa cells with high levels of ATF6α expression are resistant to ferroptosis, and genetic and pharmacological inhibition of ATF6α could, therefore, promote the ferroptotic death of tumor cells and delay PCa progression. Molecular analyses linked ATF6α regulation of ferroptosis to the PLA2G4A-mediated release of AA and the resulting increase in PGE2 production, the latter of which acts as an antiferroptotic factor.
conclusionsThis study defines ATF6α as a novel antiferroptotic regulator that exacerbates PCa progression. In addition, our data establish ATF6α-PLA2G4A signaling as an important pathological pathway in PCa, and targeting this pathway may be a novel treatment strategy.
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