ArticleSignal transduction and targeted therapy2021
AHR mediates the aflatoxin B1 toxicity associated with hepatocellular carcinoma.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 118 citations in OpenAlex.
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Balancing Nutritional Value and Food Safety in Peanut Butter: The Role of Food Matrix Characteristics in Hazard Behavior and Risk Management.Foods (Basel, Switzerland) · 2026Review
- Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Dissecting conserved molecular mechanisms of biological toxin activity through CRISPR screening.Biochemical Society transactions · 2026Review
- CRISPR Screening in Hepatocellular Carcinoma: From Tumor Progression to Immune Evasion and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Review
- Role of insulin-like growth factor/receptor signaling in hepatocellular carcinoma.Hepatology forum · 2026Review
- Case report: A case series report: recurrent urolithiasis as a risk factor for upper tract urothelial carcinoma.Frontiers in oncology · 2026Article
- Article
- Mycotoxin Contamination: Occurrence, Biotransformation, Pathogenic Mechanisms, and Strategies for Nutritional Intervention.Molecules (Basel, Switzerland) · 2025Review
- 4-Methylesculetin alleviated aflatoxin B1-induced liver injury and ferritinophagy through AMPK- TOR-Ulk axis in grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Immunological Landscape and Molecular Therapeutic Targets of the Tumor Microenvironment in Hepatocellular Carcinoma.International journal of molecular sciences · 2025Review
- Lifestyle factors in hepatocellular carcinoma: From pathogenesis to prognosis.World journal of clinical oncology · 2025Review
- Research Progress and Management Strategies for the Common Mycotoxin Contamination of Traditional Chinese Medicines.Journal of fungi (Basel, Switzerland) · 2025Review
- Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment.Cancer cell international · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Article
- Fungi and cancer: unveiling the complex role of fungal infections in tumor biology and therapeutic resistance.Frontiers in cellular and infection microbiology · 2025Review
- AhR governs lipid metabolism: the role of gut microbiota.Frontiers in microbiology · 2025Review
- A landscape review with novel criteria to evaluate microbial drivers for cancer: priorities for innovative research targeting excessive cancer mortality in sub-Saharan Africa.Frontiers in cellular and infection microbiology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma (HCC) in individuals infected with the hepatitis virus. However, the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined. Here, we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1 (AFB1) targets. Among the most significant hits was the aryl hydrocarbon receptor (AHR), a ligand-binding transcription factor regulating cell metabolism, differentiation, and immunity. AHR-deficient cells tolerated high concentrations of AFB1, in which AFB1 adduct formation was significantly decreased. AFB1 triggered AHR nuclear translocation by directly binding to its N-terminus. Furthermore, AHR mediated the expression of P450 induced by AFB1. AHR expression was also elevated in primary tumor sections obtained from AFB1-HCC patients, which paralleled the upregulation of PD-L1, a clinically relevant immune regulator. Finally, anti-PD-L1 therapy exhibited greater efficacy in HCC xenografts derived from cells with ectopic expression of AHR. These results demonstrated that AHR was required for the AFB1 toxicity associated with HCC, and implicate the immunosuppressive regimen of anti-PD-L1 as a therapeutic option for the treatment of AFB1-associated HCCs.
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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.