ArticleOncotarget2015
FXR induces SOCS3 and suppresses hepatocellular carcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
33 citing papers in PubMed, 50 citations in OpenAlex.
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non-Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers.Clinical pharmacology in drug development · 2020Trial
- Integrating single-cell RNA sequencing and artificial intelligence for multitargeted drug design for combating resistance in liver cancer.NPJ precision oncology · 2025Article
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology.The American journal of pathology · 2025Review
- Farnesoid X Receptor Attenuates the Tumorigenicity of Liver Cancer Stem Cells by Inhibiting STAT3 Phosphorylation.International journal of molecular sciences · 2025Article
- Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Current Perspectives on the Molecular and Clinical Relationships between Primary Biliary Cholangitis and Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Organoid-on-a-chip model of human ARPKD reveals mechanosensing pathomechanisms for drug discovery.Science advances · 2022Article
- Pleiotropic roles of FXR in liver and colorectal cancers.Molecular and cellular endocrinology · 2022Article
- How cancer cells remodel lipid metabolism: strategies targeting transcription factors.Lipids in health and disease · 2021Review
- Bile acid receptors and signaling crosstalk in the liver, gut and brain.Liver research (Beijing, China) · 2021Review
- Review
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- Farnesoid X Receptor Activation Impairs Liver Progenitor Cell-Mediated Liver Regeneration via the PTEN-PI3K-AKT-mTOR Axis in Zebrafish.Hepatology (Baltimore, Md.) · 2021Article
- The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2021Review
- Transcriptome analysis of sinensetin-treated liver cancer cells guided by biological network analysis.Oncology letters · 2021Article
- The Nuclear Farnesoid X Receptor Reduces p53 Ubiquitination and Inhibits Cervical Cancer Cell Proliferation.Frontiers in cell and developmental biology · 2021Article
- Activation of FXR Suppresses Esophageal Squamous Cell Carcinoma Through Antagonizing ERK1/2 Signaling Pathway.Cancer management and research · 2021Article
- Farnesoid X receptor activation induces antitumour activity in colorectal cancer by suppressing JAK2/STAT3 signalling via transactivation of SOCS3 gene.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suppressor of cytokine signaling 3 (SOCS3) is regarded as a vital repressor in the liver carcinogenesis mainly by inhibiting signal transducer and activator of transcription 3 (STAT3) activity. Farnesoid X Receptor (FXR), highly expressed in liver, has an important role in protecting against hepatocellular carcinoma (HCC). However, it is unclear whether the tumor suppressive activity of FXR involves the regulation of SOCS3. In the present study, we found that activation of FXR by its specific agonist GW4064 in HCC cells inhibited cell growth, induced cell cycle arrest at G1 phase, elevated p21 expression and repressed STAT3 activity. The above anti-tumor effects of FXR were dramatically alleviated by knockdown of SOCS3 with siRNA. Reporter assay revealed that FXR activation enhanced the transcriptional activity of SOCS3 promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay displayed that FXR directly bound to IR9 DNA motif within SOCS3 promoter region. The in vivo study in nude mice showed that treatment with FXR ligand GW4064 could decelerate the growth of HCC xenografts, up-regulate SOCS3 and p21 expression and inhibit STAT3 phosphorylation in the xenografts. These results suggest that induction of SOCS3 may be a novel mechanism by which FXR exerts its anti-HCC effects, and the FXR-SOCS3 signaling may serve as a new potential target for the prevention/treatment of HCC.
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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.