Farnesoid X Receptor Activation Enhances Transforming Growth Factor β-Induced Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells
| Autor: | Makoto Makishima, Keiji Sano, Masahiko Kainuma, Ichiro Takada |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Receptors Cytoplasmic and Nuclear epithelial–mesenchymal transition lcsh:Chemistry chemistry.chemical_compound Chenodeoxycholic acid Receptor transforming growth factor β lcsh:QH301-705.5 Spectroscopy Bile acid Liver Neoplasms Obeticholic acid General Medicine hepatocellular carcinoma Cadherins Computer Science Applications Gene Expression Regulation Neoplastic Liver Carcinoma Hepatocellular Epithelial-Mesenchymal Transition medicine.drug_class guggulsterone Chenodeoxycholic Acid Catalysis Article Inorganic Chemistry Bile Acids and Salts Transforming Growth Factor beta1 03 medical and health sciences Cell Line Tumor medicine Humans bile acid Epithelial–mesenchymal transition Physical and Theoretical Chemistry Molecular Biology N-cadherin Organic Chemistry focal adhesion kinase Isoxazoles digestive system diseases 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 chemistry Cancer research Farnesoid X receptor Guggulsterone farnesoid X receptor Transforming growth factor |
| Zdroj: | International Journal of Molecular Sciences Volume 19 Issue 7 International Journal of Molecular Sciences, Vol 19, Iss 7, p 1898 (2018) |
| ISSN: | 1422-0067 |
| Popis: | Farnesoid X receptor (FXR) is a receptor for bile acids and plays an important role in the regulation of bile acid metabolism in the liver. Although FXR has been shown to affect hepatocarcinogenesis through both direct and indirect mechanisms, potential roles of FXR in epithelial&ndash mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remain unclear. We examined the effect of several FXR ligands on EMT-related morphological changes in HCC cell lines, such as HuH-7 and Hep3B cells. FXR agonists (chenodeoxycholic acid, GW4064, and obeticholic acid)&mdash but not an antagonist (guggulsterone)&mdash induced actin polymerization and expression of N-cadherin and phosphorylated focal adhesion kinase, although they were less effective than transforming growth factor &beta (TGF-&beta ). FXR agonist treatment enhanced TGF-&beta induced EMT morphologic changes and FXR antagonist inhibited the effect of TGF-&beta Thus, FXR activation enhances EMT in HCC and FXR antagonists may be EMT-suppressing drug candidates. |
| Databáze: | OpenAIRE |
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