title: βKlotho suppresses tumor growth in hepatocellular carcinoma by regulating Akt/GSK-3β/cyclin D1 signaling pathway.
abstract: βKlotho is a regulator in multiple metabolic processes, while its role in cancer remains unclear. We found the expression of βKlotho was down-regulated in human hepatocellular carcinoma tissues compared with that in paired adjacent non-tumourous liver tissues. Hepatoma cells also showed decreased expression of βKlotho compared with normal hepatocyte cells. Reintroduction of βKlotho into hepatoma cells inhibited their proliferation. The anti-proliferative effect of βKlotho might be linked with G1 to S phase arrest, which was mediated by Akt/GSK-3β/cyclin D1 signaling, since forced expression βKlotho reduced the phosphorylation level of Akt and GSK-3β and induced down-regulation of cyclin D1. Furthermore, βKlotho overexpression could inhibit tumorgenesis, while constitutively activated Akt could override the suppressive effects of βKlotho in vivo. These data suggest βKlotho suppresses tumor growth in hepatocellular carcinoma.
authors: Department of General Surgery, Lingnan Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors: Xiaoming
authors: X
authors: Ye
authors: Yu
authors: Y
authors: Guo
authors: Qi
authors: Q
authors: Zhang
authors: Wenjie
authors: W
authors: Chen
authors: Xuefeng
authors: X
authors: Hua
authors: Wei
authors: W
authors: Liu
authors: Yang
authors: Y
authors: Yang
authors: Guihua
authors: G
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D000090265:Klotho Proteins; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014183:Transplantation, Heterologous
chemical_list: D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005966:Glucuronidase; D000090265:Klotho Proteins
references: Nat Rev Cancer. 2009 Mar;9(3):153-66
references: 19238148
references: World J Gastroenterol. 2007 Feb 7;13(5):683-91
references: 17278190
references: Hepatology. 2006 Jan;43(1):191-3
references: 16374861
references: Mol Cancer. 2012 Mar 23;11:14
references: 22439738
references: Mol Cell Endocrinol. 2009 Feb 5;299(1):72-8
references: 19063940
references: Nature. 1999 Apr 1;398(6726):422-6
references: 10201372
references: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references: 18287387
references: J Clin Invest. 2005 Aug;115(8):2202-8
references: 16075061
references: J Gastroenterol. 1999 Aug;34(4):486-93
references: 10452682
references: J Biol Chem. 2010 Sep 24;285(39):30069-78
references: 20657013
references: Science. 1996 Dec 6;274(5293):1672-7
references: 8939849
references: J Biol Chem. 2000 May 19;275(20):15482-9
references: 10809780
references: J Biol Chem. 2007 Sep 14;282(37):26687-26695
references: 17623664
references: Hepatogastroenterology. 1998 Sep-Oct;45(23):1635-42
references: 9840120
references: Mol Carcinog. 2009 Jun;48(6):553-62
references: 19009564
references: Endocr Rev. 2000 Jun;21(3):215-44
references: 10857553
references: Horm Metab Res. 2003 Nov-Dec;35(11-12):685-93
references: 14710347
references: Cancer Sci. 2007 May;98(5):629-35
references: 17359287
references: Nature. 2004 Nov 18;432(7015):316-23
references: 15549093
references: Cancer Lett. 2003 Jun 10;195(2):127-37
references: 12767520
references: Cancer Res. 2001 Jul 15;61(14):5389-95
references: 11454681
references: Mech Dev. 2000 Nov;98(1-2):115-9
references: 11044614
references: J Gastroenterol. 2005 Mar;40(3):225-35
references: 15830281
references: Cancer Lett. 2011 Aug 1;307(1):93-103
references: 21504839
references: Cell Signal. 2008 Apr;20(4):581-9
references: 18023328
references: J Biol Chem. 1999 May 28;274(22):15947-52
references: 10336501
references: Curr Cancer Drug Targets. 2006 Dec;6(8):681-9
references: 17168673
references: Cancer Res. 2007 Feb 1;67(3):863-7
references: 17283114
references: J Biol Chem. 2007 Sep 14;282(37):27277-27284
references: 17627937
references: J Cell Biochem Suppl. 1996;25:23-8
references: 9027594
references: Genes Dev. 1998 Nov 15;12(22):3499-511
references: 9832503
references: Cancer Res. 1994 Jun 15;54(12):3107-10
references: 8205525