ArticleCell death & disease2025
AKR1C3 enhances radioresistance in esophageal adenocarcinoma via inhibiting ferroptosis through suppressing TRIM21-mediated ubiquitination of HSPA5.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The trial behind it
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
9 citing papers in PubMed.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Triphala Targets the SLC7A11-GSH-GPX4 Axis to Trigger Ferroptosis in Oral Cancer: An Integrated Network Pharmacology, Molecular Docking, and Experimental Validation Study.Chemical biology & drug design · 2026Article
- Review
- Targeting the CAF-GDF15 axis attenuates AKT-mediated mitochondrial rewiring and chemoradiation resistance in esophageal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Recapitulating the tumour microenvironment: advancing personalised radiation therapy through organoid technology.Journal of experimental & clinical cancer research : CR · 2026Review
- Natural simple coumarins and their interaction with AKR1C3: implications for overcoming chemoradioresistance in gastrointestinal carcinomas.Medical oncology (Northwood, London, England) · 2026Article
- Environmental Lead Promotes Breast Cancer Migration and Invasion via the AKR1C3-NF-κB-MMP Axis.Biomedicines · 2026Article
- Targeting ferroptosis and cuproptosis in gastrointestinal cancers: molecular mechanisms, metabolic vulnerabilities, and therapeutic interventions.Molecular biomedicine · 2025Review
- Advances in esophageal organoids: from construction to applications.Journal of tissue engineeringReview
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Esophageal adenocarcinoma (EAC) is the predominant subtype of esophageal cancer (EC) in high-income countries, and radioresistance is one of the key factors for the poor prognosis. In this study, we successfully established a radioresistant EAC in vitro model. Aldo-keto reductase 1C3 (AKR1C3) was identified as a promising regulator of radioresistance by RNA-seq analysis and subsequent functional studies. Through integrated analyses of scRNA-seq and TCGA datasets, we found that AKR1C3 was likely to enhance radioresistance by inhibition of ferroptosis. Indeed, analysis of the lipid ROS level by C11-Bodipy staining and the result of transmission electron microscopy revealed that AKR1C3 could prevent EAC cells from ferroptosis. Mechanistically, AKR1C3 binds to the nucleotide-binding domain of HSPA5, thereby inhibiting the E3 ligase TRIM21-induced ubiquitin-dependent proteasomal degradation of HSPA5, which further stabilizes GPX4, thus inhibiting ferroptosis. Importantly, AKR1C3 inhibitor resensitized the EAC patient-derived organoids to radiotherapy. In conclusion, this study highlights AKR1C3 as a regulator of radioresistance and a potential therapeutic target in EAC.
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Registered trials
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 Socratic graph.