ArticleCell death and differentiation2025
The AKR1C1-CYP1B1-cAMP signaling axis controls tumorigenicity and ferroptosis susceptibility of extrahepatic cholangiocarcinoma.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Selenoprotein thioredoxin reductase 1 promotes cancer cells ferroptosis by suppressing GPX4 expression.Cell death and differentiation · 2026Article
- Multi-algorithm machine learning combined with in silico gene knockout reveals the diagnostic value and functional regulatory networks of ferroptosis-related genes in gastric cancer.Translational cancer research · 2026Article
- PRDX1 depletion predisposes to ferroptosis through inhibiting the cAMP pathway in B-cell acute lymphoblastic leukemia.Cancer gene therapy · 2026Article
- Inhibition of Calcium-Dependent Lipid Droplets Relocation of ACSL4-PKCβ-ALOX15 Complex Alleviates Ferroptosis and Acute Pancreatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression.Cell death & disease · 2026Article
- Curcumin pretreatment enhances the capacity of BMSC exosomes to attenuate renal ischemia-reperfusion injury by ferroptosis suppression via miR-16-5p/Smad3/Mb axis.Stem cell research & therapy · 2026Article
- Calycosin Targets the CYP1B1-AKT/SP1-GPX4 Axis to Modulate Ferroptosis in Colorectal Carcinogenesis.Phytotherapy research : PTR · 2026Article
- Targeting AKR1B1 reprograms tumor-associated macrophages to enhance antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- The Multilayered Landscape of Ferroptosis: Plasticity, Propagation, and Evolutionary Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Patchouli alcohol triggers autophagic cell death in non-small cell lung cancer cells through targeting GNAI1 to dissociate the GNAI1/ARRB1 complex.International journal of biological sciences · 2026Article
- Ferroptosis in biliary tract cancer: Molecular mechanisms and therapeutic applications (Review).International journal of oncology · 2026Review
- Characterization of Differential GPX4 Essentiality Between Intrahepatic and Extrahepatic Cholangiocarcinoma via Leveraging of a Large-Scale Functional Genomic Screen.International journal of molecular sciences · 2025Article
- Cytochrome P450 (CYP) 1 enzymes in acute lung injury: from molecular insights to therapeutic implications.Redox report : communications in free radical research · 2025Review
- Potential role of AhR in ischemia‑reperfusion injury and cancers: Focus on ferroptosis and lipid peroxidation signaling pathways (Review).International journal of molecular medicine · 2025Review
- Molecular mechanisms and genetic features of cholangiocarcinoma: implications for targeted therapeutic strategies.Precision clinical medicine · 2025Review
- SUMO2 inhibits ACSL3 protein degradation to antagonize erastin-induced ferroptosis in hepatocellular carcinoma.Discover oncology · 2025Article
- KLF9, Epigenetic Silenced by DNMT1, Promotes ERK-Mediated Ferroptosis of Osteoarthritic Chondrocytes Through Transcriptionally Regulating CYP1B1.Journal of cellular and molecular medicine · 2025Article
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11 authors.
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Abstract
Extrahepatic cholangiocarcinoma (ECC), a highly malignant type of cancer with increasing incidence, has a poor prognosis due to limited treatment options. Based on genomic analysis of ECC patient samples, here we report that aldo-keto reductase family 1 member C1 (AKR1C1) is highly expressed in human ECC tissues and closely associated with ECC progression and poor prognosis. Intriguingly, we show that inducible AKR1C1 knockdown triggers ECC cells to undergo ferroptosis. Mechanistically, AKR1C1 degrades the protein stability of the cytochrome P450 family member CYP1B1, a newly discovered mediator of ferroptosis, via ubiquitin-proteasomal degradation. Additionally, AKR1C1 decreases CYP1B1 mRNA level through the transcriptional factor aryl-hydrocarbon receptor (AHR). Furthermore, the AKR1C1-CYP1B1 axis modulates ferroptosis in ECC cells via the cAMP-PKA signaling pathway. Finally, in a xenograft mouse model of ECC, AKR1C1 depletion sensitizes cancer cells to ferroptosis and synergizes with ferroptosis inducers to suppress tumor growth. Therefore, the AKR1C1-CYP1B1-cAMP signaling axis is a promising therapeutic target for ECC treatment, especially in combination with ferroptosis inducers.
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