ArticlePloS one2015
Reciprocal interaction of Wnt and RXR-α pathways in hepatocyte development and hepatocellular carcinoma.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Novel therapeutic strategies for targeting fatty acid oxidation in cancer.Biomarker research · 2025Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Wnt/β-catenin signaling as an emerging potential key pharmacological target in cholangiocarcinoma.Bioscience reports · 2020Review
- Decellularized human liver extracellular matrix (hDLM)-mediated hepatic differentiation of human induced pluripotent stem cells (hIPSCs).Journal of tissue engineering and regenerative medicine · 2018Article
- A genome-wide interactome of DNA-associated proteins in the human liver.Genome research · 2017Article
- SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism.Molecular oncology · 2016Article
- Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer.Cell death & disease · 2016Review
- Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.Molecular cancer therapeutics · 2016Article
- Effects of LG268 on Cell Proliferation and Apoptosis of NB4 Cells.International journal of medical sciences · 2016Article
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Authors and funding
13 authors.
Funding
Abstract
Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal development. We found a major shift in expression of Wnt and RXR-α pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-α gene signature categorized HCCs into two subtypes (high Wnt, low RXR-α and low Wnt, high RXR-α), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-α levels in hepatocytes increased Wnt signaling and enhanced tumorigenicity, whereas ligand activation of RXR-α achieved the opposite. These results corroborate that there are two main HCC subtypes that correspond to the degree of hepatocyte differentation and that RXR-α, in part via Wnt signaling, plays a key functional role in the hepatocyte-like subtype and potentially could serve as a selective therapeutic target.
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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.