ArticleJCI insight2024
SLC4A11 mediates ammonia import and promotes cancer stemness in hepatocellular carcinoma.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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
13 citing papers in PubMed.
- Article
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- Impaired nitrogenous waste clearance promotes hepatocellular carcinoma.Science advances · 2026Article
- Ammonia metabolic reprogramming in the tumor microenvironment: emergence of an immunosuppressive niche.Frontiers in cell and developmental biology · 2026Review
- Ammonia signaling network: the intersection of tumor metabolism, epigenetics, and metastasis.Frontiers in endocrinology · 2026Review
- Ammonia in cancer: dual roles and therapeutic strategies.Cancer cell international · 2025Review
- SLC4A11 is a targetable marker correlated with therapeutic responses in ovarian cancer.Journal of ovarian research · 2025Article
- Review
- Anxiety is a risk prognosis factor for hepatocellular carcinoma with portal vein tumor thrombus who underwent hepatic arterial infusion chemotherapy: a propensity score-matching cohort study.World journal of surgical oncology · 2025Article
- High-ammonia microenvironment promotes stemness and metastatic potential in hepatocellular carcinoma through metabolic reprogramming.Discover oncology · 2025Article
- The ammonia-Slc4a11 axis in T cells alleviates LPS-induced mastitis.Frontiers in immunology · 2025Article
- Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.Frontiers in oncology · 2025Review
- Integrating single cell analysis and machine learning methods reveals stem cell-related gene S100A10 as an important target for prediction of liver cancer diagnosis and immunotherapy.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
31 authors.
Funding
Abstract
End-stage liver disease is marked by portal hypertension, systemic elevations in ammonia, and development of hepatocellular carcinoma (HCC). While these clinical consequences of cirrhosis are well described, it remains poorly understood whether hepatic insufficiency and the accompanying elevations in ammonia contribute to HCC carcinogenesis. Using preclinical models, we discovered that ammonia entered the cell through the transporter SLC4A11 and served as a nitrogen source for amino acid and nucleotide biosynthesis. Elevated ammonia promoted cancer stem cell properties in vitro and tumor initiation in vivo. Enhancing ammonia clearance reduced HCC stemness and tumor growth. In patients, elevations in serum ammonia were associated with an increased incidence of HCC. Taken together, this study forms the foundation for clinical investigations using ammonia-lowering agents as potential therapies to mitigate HCC incidence and aggressiveness.
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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 OpenQuestion graph.