ArticleThe American journal of pathology2017
Thyroid Hormone Receptor-β Agonist GC-1 Inhibits Met-β-Catenin-Driven Hepatocellular Cancer.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacotherapy in metabolic-dysfunction-associated steatotic liver disease: an updated review of the past, present and a promising future.Diabetology international · 2025Article
- LiverClear: A versatile protocol for mouse liver tissue clearing.STAR protocols · 2022Article
- Development of Thyroid Hormones and Synthetic Thyromimetics in Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Wnt/-Catenin Signaling and Liver Regeneration: Circuit, Biology, and Opportunities.Gene expression · 2021Review
- Basic science to clinical trials in non-alcoholic fatty liver disease and alcohol-related liver disease: collaboration with industry.Translational gastroenterology and hepatology · 2021Review
- Review
- Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival.BMC cancer · 2020Article
- Thyroid Hormone Analogues: An Update.Thyroid : official journal of the American Thyroid Association · 2020Review
- Potential role of two novel agonists of thyroid hormone receptor-β on liver regeneration.Cell proliferation · 2020Article
- Thyroid Hormone in Hepatocellular Carcinoma: Cancer Risk, Growth Regulation, and Anticancer Drug Resistance.Frontiers in medicine · 2020Review
- Current and Emerging Approaches for Nonalcoholic Steatohepatitis Treatment.Gene expression · 2019Review
- Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations.Cell metabolism · 2019Article
- Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases.Journal of biomedical science · 2019Review
- Dual ablation of β- and γ-catenin: Critical regulators of junctions and their functions.Hepatology (Baltimore, Md.) · 2018Article
- The Effect of Selective c-MET Inhibitor on Hepatocellular Carcinoma in the MET-Active, β-Catenin-Mutated Mouse Model.Gene expression · 2018Article
- Thyroid Hormones, Thyromimetics and Their Metabolites in the Treatment of Liver Disease.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The thyromimetic agent GC-1 induces hepatocyte proliferation via Wnt/β-catenin signaling and may promote regeneration in both acute and chronic liver insufficiencies. However, β-catenin activation due to mutations in CTNNB1 is seen in a subset of hepatocellular carcinomas (HCC). Thus, it is critical to address any effect of GC-1 on HCC growth and development before its use can be advocated to stimulate regeneration in chronic liver diseases. In this study, we first examined the effect of GC-1 on β-catenin-T cell factor 4 activity in HCC cell lines harboring wild-type or mutated-CTNNB1. Next, we assessed the effect of GC-1 on HCC in FVB mice generated by hydrodynamic tail vein injection of hMet-S45Y-β-catenin, using the sleeping beauty transposon-transposase. Four weeks following injection, mice were fed 5 mg/kg GC-1 or basal diet for 10 or 21 days. GC-1 treatment showed no effect on β-catenin-T cell factor 4 activity in HCC cells, irrespective of CTNNB1 mutations. Treatment with GC-1 for 10 or 21 days led to a significant reduction in tumor burden, associated with decreased tumor cell proliferation and dramatic decreases in phospho-(p-)Met (Y1234/1235), p-extracellular signal-related kinase, and p-STAT3 without affecting β-catenin and its downstream targets. GC-1 exerts a notable antitumoral effect on hMet-S45Y-β-catenin HCC by inactivating Met signaling. GC-1 does not promote β-catenin activation in HCC. Thus, GC-1 may be safe for use in inducing regeneration during chronic hepatic insufficiency.
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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.