title: Succinate dehydrogenase 5 (SDH5) regulates glycogen synthase kinase 3β-β-catenin-mediated lung cancer metastasis.
abstract: We demonstrate that loss of succinate dehydrogenase 5 (SDH5) expression initiates epithelial-mesenchymal transition (EMT), which is visualized by the repression of E-cadherin and up-regulation of vimentin in lung cancer cell lines and clinical lung cancer specimens. In SDH5 knock-out mice, lung epithelial cells exhibited elevated mesenchymal markers, which is characteristic of EMT. Using a human lung xenograft-mouse model, we observed that knocking down endogenous SDH5 in human carcinoma cells leads to the development of multiple lymph node metastases. Moreover, our data indicate that SDH5 functions as a critical protein in regulating EMT by modulating the glycogen synthase kinase (GSK)-3β-β-catenin signaling pathway. These results reveal a critical role for SDH5 in EMT and suggest that SDH5 may be a prognostic biomarker and potential therapeutic target for lung cancer metastasis.
authors: From the Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors: Jun
authors: J
authors: Liu
authors: Liuwei
authors: L
authors: Gao
authors: Hua
authors: H
authors: Zhang
authors: Daowei
authors: D
authors: Wang
authors: Meng
authors: M
authors: Wang
authors: Jianquan
authors: J
authors: Zhu
authors: Cong
authors: C
authors: Pang
authors: Changli
authors: C
authors: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D018613:Microscopy, Confocal; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; C543341:SDHAF2 protein, human; D051176:beta Catenin; D013385:Succinate Dehydrogenase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D054648:Protein Phosphatase 2
keywords: Biomarkers; E-cadherin; EMT; Lung Cancer; Metastasis; Mitochondrial Protein; SDH5
references: Clin Cancer Res. 2011 Jan 15;17(2):247-54
references: 21224366
references: Hepatology. 2009 Nov;50(5):1464-74
references: 19821482
references: Science. 2009 Aug 28;325(5944):1139-42
references: 19628817
references: PLoS One. 2011;6(10):e27053
references: 22046442
references: Nature. 2012 Mar 18;483(7391):613-7
references: 22425996
references: J Biol Chem. 2011 May 6;286(18):16218-28
references: 21454711
references: Oncogene. 2011 Mar 24;30(12):1436-48
references: 21057535
references: Cancer Cell. 2009 Sep 8;16(3):180-2
references: 19732718
references: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20900-5
references: 19106302
references: Lung Cancer. 2013 Jan;79(1):54-8
references: 23131495
references: Lung Cancer. 2012 Nov;78(2):161-6
references: 22959241
references: Lung Cancer. 2013 Jan;79(1):1-7
references: 23137549
references: FASEB J. 2005 Jun;19(8):1048-50
references: 15788447
references: BMC Cancer. 2010 Feb 23;10:58
references: 20178594
references: J Biol Chem. 2012 May 18;287(21):17746-17753
references: 22457351
references: Oncogene. 2010 Oct 21;29(42):5741-54
references: 20697346
references: Clin Cancer Res. 2012 Nov 15;18(22):6356-63
references: 23014530
references: Science. 2012 Jan 20;335(6066):282-3
references: 22267789
references: Gut. 2012 May;61(5):714-24
references: 21873734
references: Oncogene. 2011 Mar 24;30(12):1449-59
references: 21102519
references: Mol Cell Biochem. 2011 Mar;349(1-2):33-40
references: 21116689
references: J Immunol. 2011 Dec 15;187(12):6539-49
references: 22095718
references: Cancer Res. 2011 Feb 15;71(4):1235-43
references: 21159661
references: Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15858-63
references: 21911394
references: Endocrine. 2010 Dec;38(3):397-401
references: 20972721
references: Hepatology. 2009 May;49(5):1515-24
references: 19205031
references: J Appl Physiol (1985). 2011 Apr;110(4):892-900
references: 21193562