ArticleThe Journal of clinical investigation2023
RB1-deficient prostate tumor growth and metastasis are vulnerable to ferroptosis induction via the E2F/ACSL4 axis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Targeting NDUFS4 Disrupts Oxidative Phosphorylation and Induces Ferroptosis in Olaparib-Resistant Prostate Cancer.Molecular cancer therapeutics · 2026Article
- Ferroptosis at the Metabolic-Immune Interface in Metastatic Castration-Resistant Prostate Cancer: Mechanistic Evidence, Translational Gaps, and Combination Strategies.Annals of surgical oncology · 2026Review
- Ferroptosis and prostate cancer: A translational path from molecular mechanisms to precision therapy.Genes & diseases · 2026Review
- Histone chaperone HIRA restrains ferroptosis susceptibility through epigenetic control of iron metabolism in prostate cancer.Science China. Life sciences · 2026Article
- Pre-diagnostic metabolites in peripheral blood of Langerhans cell histiocytosis children with posterior pituitary involvement.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- ACSS2 Suppresses Ferroptosis to Drive Breast Cancer Brain Metastasis.Cancer research · 2026Article
- Proteomic Analysis Reveals AMPKα-Mediated Antiandrogen Resistance via Ferroptosis Suppression in Prostate Cancer.Cancer science · 2026Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Divergent roles of SPOP and CHD1 in ACSL4 regulation reveal context-dependent vulnerabilities for targeting ferroptosis.Nature communications · 2026Article
- CoQExperimental & molecular medicine · 2026Review
- Exploring multiple biomarkers and constructing ferroptosis-associated competing endogenous RNA networks as dual targets in retinoblastoma.Oncology letters · 2026Article
- Ferroptosis vulnerability of enzalutamide resistant prostate cancer conferred by ACSL4 overexpression and GPX4 antagonism.Cell death & disease · 2026Article
- Therapeutic translation of traditional Chinese medicine Huangqi derived exosome like nanoparticles: targeting prostate cancer through ferroptosis activation, immune reprogramming, and microbiome modulation.Journal of nanobiotechnology · 2026Article
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Lipids grease the chain of cancer progression.Trends in cancer · 2026Review
- The multifaceted roles of the ACSL family in cancer: Metabolic reprogramming, ferroptosis regulation and tumour immune microenvironment remodelling.Clinical and translational medicine · 2026Review
- Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application.Antioxidants (Basel, Switzerland) · 2026Review
- Exploiting metabolic cell death for cancer therapy.Nature reviews. Cancer · 2026Review
- Lipid remodeling and ferroptosis in phosphatidylcholine-mediated tumor-stroma crosstalk.Frontiers in molecular biosciences · 2026Review
- The role of SALL1-MGST1 axis-mediated ferroptosis inhibition in chemoresistance of retinoblastoma.PloS one · 2026Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Inactivation of the RB1 tumor suppressor gene is common in several types of therapy-resistant cancers, including metastatic castration-resistant prostate cancer, and predicts poor clinical outcomes. Effective therapeutic strategies against RB1-deficient cancers remain elusive. Here, we showed that RB1 loss/E2F activation sensitized cancer cells to ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, by upregulating expression of ACSL4 and enriching ACSL4-dependent arachidonic acid-containing phospholipids, which are key components of ferroptosis execution. ACSL4 appeared to be a direct E2F target gene and was critical to RB1 loss-induced sensitization to ferroptosis. Importantly, using cell line-derived xenografts and genetically engineered tumor models, we demonstrated that induction of ferroptosis in vivo by JKE-1674, a highly selective and stable GPX4 inhibitor, blocked RB1-deficient prostate tumor growth and metastasis and led to improved survival of the mice. Thus, our findings uncover an RB/E2F/ACSL4 molecular axis that governs ferroptosis and also suggest a promising approach for the treatment of RB1-deficient malignancies.
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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.