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Farnesoid X Receptor Activation Enhances Transforming Growth Factor β-Induced Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2018 Jun 28; Vol. 19 (7). Date of Electronic Publication: 2018 Jun 28. - Publication Year :
- 2018
-
Abstract
- 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–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)—but not an antagonist (guggulsterone)—induced actin polymerization and expression of N-cadherin and phosphorylated focal adhesion kinase, although they were less effective than transforming growth factor β (TGF-β). FXR agonist treatment enhanced TGF-β-induced EMT morphologic changes and FXR antagonist inhibited the effect of TGF-β. Thus, FXR activation enhances EMT in HCC and FXR antagonists may be EMT-suppressing drug candidates.
- Subjects :
- Bile Acids and Salts metabolism
Cadherins genetics
Carcinoma, Hepatocellular drug therapy
Carcinoma, Hepatocellular pathology
Cell Line, Tumor
Chenodeoxycholic Acid analogs & derivatives
Chenodeoxycholic Acid pharmacology
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic drug effects
Humans
Isoxazoles pharmacology
Liver drug effects
Liver metabolism
Liver Neoplasms drug therapy
Liver Neoplasms pathology
Receptors, Cytoplasmic and Nuclear agonists
Receptors, Cytoplasmic and Nuclear antagonists & inhibitors
Carcinoma, Hepatocellular genetics
Liver Neoplasms genetics
Receptors, Cytoplasmic and Nuclear genetics
Transforming Growth Factor beta1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 19
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 29958417
- Full Text :
- https://doi.org/10.3390/ijms19071898