title: Farnesoid X receptor associates with β-catenin and inhibits its activity in hepatocellular carcinoma.
abstract: The association between the temporal activation of Wnt/β-catenin pathway and the spontaneous hepatocellular carcinoma (HCC) development in Farnesoid X receptor (FXR) knockout mice is not well understood. We found that Huh7 cells depleted with FXR by RNAi showed enhanced cell growth, migration and invasion in vitro and accelerated tumor xenografts formation in nude mice. And these phenotypes were attenuated by simultaneous knockdown of β-catenin with RNAi. Furthermore, we identified that FXR could bind with β-Catenin through AF1 domain, and disrupt the assembly of the core β-Catenin/TCF4 complex. Activation of FXR attenuated the DNA-binding activity of β-Catenin/TCF4, and subsequently, its targeting gene-cyclin D1 expression. Importantly, FXR expression was markedly reduced in human HCC, an event which correlated with aberrant activation of β-Catenin. These data identified FXR as a negative regulator of HCC development through direct suppression of Wnt/β-catenin pathway.
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical college, Fudan University, Shanghai, China.
authors: Xijun
authors: X
authors: Liu
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical college, Fudan University, Shanghai, China.
authors: Xingwang
authors: X
authors: Zhang
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical college, Fudan University, Shanghai, China.
authors: Lingling
authors: L
authors: Ji
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical college, Fudan University, Shanghai, China.
authors: Jianxin
authors: J
authors: Gu
authors: Department of Radiology, Zhongshan Hospital of Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, China.
authors: Meiling
authors: M
authors: Zhou
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical college, Fudan University, Shanghai, China.
authors: She
authors: S
authors: Chen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051176:beta Catenin; D000099150:Receptor, Farnesoid X-Activated
references: Cancer. 2001 Jul 1;92(1):136-45
references: 11443619
references: Gastroenterology. 2001 Jun;120(7):1763-73
references: 11375957
references: Cell. 1995 Jun 2;81(5):687-93
references: 7774010
references: Science. 1997 Mar 21;275(5307):1787-90
references: 9065402
references: Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8847-51
references: 9671767
references: Liver Int. 2005 Feb;25(1):70-6
references: 15698401
references: J Clin Pathol. 2005 Mar;58(3):225-36
references: 15735151
references: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2020-30
references: 16037564
references: Endocr Rev. 2005 Dec;26(7):898-915
references: 16126938
references: Cell. 2006 Nov 3;127(3):469-80
references: 17081971
references: Cancer Res. 2007 Feb 1;67(3):863-7
references: 17283114
references: Carcinogenesis. 2007 May;28(5):940-6
references: 17183066
references: Hepatology. 2007 May;45(5):1298-305
references: 17464972
references: Gastroenterology. 2007 Jun;132(7):2557-76
references: 17570226
references: Hepatology. 2008 Jul;48(1):289-98
references: 18537191
references: Future Oncol. 2008 Oct;4(5):647-60
references: 18922122
references: Cell Res. 2008 Nov;18(11):1087-95
references: 18825165
references: J Pharmacol Exp Ther. 2011 Jul;338(1):12-21
references: 21430080
references: Oncogene. 2011 Sep 29;30(39):4129-40
references: 21499302
references: N Engl J Med. 2011 Sep 22;365(12):1118-27
references: 21992124
references: J Hematol Oncol. 2011;4:41
references: 21988803
references: Gene. 2012 Feb 1;493(1):44-51
references: 22146319
references: Mol Endocrinol. 2012 Jan;26(1):37-51
references: 22108803
references: Int J Cancer. 2012 May 15;130(10):2232-9
references: 21780109
references: J Hepatol. 2013 Nov;59(5):1107-17
references: 23835194
references: Biochem Biophys Res Commun. 2014 Jan 3;443(1):211-6
references: 24291500
references: Curr Biol. 1999 Dec 2;9(23):1415-8
references: 10607566
references: Mol Endocrinol. 2012 May;26(5):775-85
references: 22474109
references: Nat Genet. 2012 Jun;44(6):694-8
references: 22561517
references: Dig Dis Sci. 2004 Jun;49(6):982-9
references: 15309887
references: PLoS One. 2012;7(10):e43044
references: 23056173
references: Mol Pharm. 2012 Jun 4;9(6):1693-704
references: 22524153