ArticleCarcinogenesis2017
FXR-Gankyrin axis is involved in development of pediatric liver cancer.
Article in Carcinogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Nuclear receptor FXR inhibits ferroptosis to alleviate hepatic ischemia-reperfusion injury by targeting GPX4 in a mouse model.Journal of molecular histology · 2025Article
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- Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring.Cellular and molecular gastroenterology and hepatology · 2024Article
- p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.Nutrients · 2023Review
- Article
- Second Generation Small Molecule Inhibitors of Gankyrin for the Treatment of Pediatric Liver Cancer.Cancers · 2022Article
- Pleiotropic roles of FXR in liver and colorectal cancers.Molecular and cellular endocrinology · 2022Article
- The differential expression of perilipin-2 in hepatoblastoma and its association with prognosis.Histology and histopathology · 2021Article
- Olaparib Inhibits Tumor Growth of Hepatoblastoma in Patient-Derived Xenograft Models.Hepatology (Baltimore, Md.) · 2021Article
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- Farnesoid X receptor via Notch1 directs asymmetric cell division of Sox9Stem cell research & therapy · 2021Article
- Molecular signatures of aggressive pediatric liver cancer.Archives of stem cell and therapy · 2021Article
- Small Molecule Cjoc42 Improves Chemo-Sensitivity and Increases Levels of Tumor Suppressor Proteins in Hepatoblastoma Cells and in Mice by Inhibiting Oncogene Gankyrin.Frontiers in pharmacology · 2021Article
- Molecular Mechanisms of Hepatoblastoma.Seminars in liver disease · 2021Article
- The "Janus" Role of C/EBPs Family Members in Cancer Progression.International journal of molecular sciences · 2020Review
- Peroxiredoxin 4 promotes embryonal hepatoblastoma cell migration but induces fetal cell differentiation.American journal of translational research · 2020Article
- The Emerging Roles of Cancer Stem Cells and Wnt/Beta-Catenin Signaling in Hepatoblastoma.Cancers · 2019Review
- Liver Proliferation Is an Essential Driver of Fibrosis in Mouse Models of Nonalcoholic Fatty Liver Disease.Hepatology communications · 2019Article
- NR6A1 regulates lipid metabolism through mammalian target of rapamycin complex 1 in HepG2 cells.Cell communication and signaling : CCS · 2019Article
- Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPα-p300 Axis.Cell reports · 2018Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins. We next analyzed FXR-Gank-Tumor suppressor pathways in a large cohort of HBL patients which include 6 controls and 53 HBL samples. Systemic analysis of these samples and RNA-Seq approach revealed that the FXR-Gank axis is activated; markers of hepatic stem cells are dramatically elevated and hepatocyte markers are reduced in HBL samples. In the course of these studies, we found that RNA binding protein CUGBP1 is a new tumor suppressor protein which is reduced in all HBL samples. Therefore, we generated CUGBP1 KO mice and examined HBL signatures in the liver of these mice. Micro-array studies revealed that the HBL-specific molecular signature is developed in livers of CUGBP1 KO mice at very early ages. Thus, we conclude that FXR-Gank-TSPs-Stem cells pathway is a key determinant of liver cancer in animal models and in pediatric liver cancer. Our data provide a strong basis for development of FXR-Gank-based therapy for treatment of patients with hepatoblastoma.
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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.