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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.

Titel:	Succinate dehydrogenase 5 (SDH5) regulates glycogen synthase kinase 3β-β-catenin-mediated lung cancer metastasis.
Autor/in / Beteiligte Person:	Liu, J ; Gao, L ; Zhang, H ; Wang, D ; Wang, M ; Zhu, J ; Pang, C ; Wang, C
Link:	Zum Volltext
Zeitschrift:	The Journal of biological chemistry, Jg. 288 (2013-10-11), Heft 41, S. 29965
Veröffentlichung:	2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology ; <i>Original Publication</i>: Baltimore, MD : American Society for Biochemistry and Molecular Biology, 2013
Medientyp:	academicJournal
ISSN:	1083-351X (electronic)
DOI:	10.1074/jbc.M113.450106
Schlagwort:	Animals Blotting, Western Cell Line, Tumor Cell Movement Epithelial-Mesenchymal Transition Glycogen Synthase Kinase 3 genetics Glycogen Synthase Kinase 3 beta Heterografts Humans Immunohistochemistry Lung Neoplasms genetics Lung Neoplasms metabolism Male Mice Mice, Knockout Mice, Nude Microscopy, Confocal Mitochondrial Proteins genetics Neoplasm Metastasis Protein Binding Protein Phosphatase 2 genetics Protein Phosphatase 2 metabolism RNA Interference Signal Transduction Succinate Dehydrogenase genetics Tumor Burden beta Catenin genetics Glycogen Synthase Kinase 3 metabolism Lung Neoplasms pathology Mitochondrial Proteins metabolism Succinate Dehydrogenase metabolism beta Catenin metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Biol Chem] 2013 Oct 11; Vol. 288 (41), pp. 29965-73. <i>Date of Electronic Publication: </i>2013 Aug 27. MeSH Terms: Glycogen Synthase Kinase 3 / metabolism ; Lung Neoplasms / pathology ; Mitochondrial Proteins / metabolism ; Succinate Dehydrogenase / metabolism ; beta Catenin / *metabolism ; Animals ; Blotting, Western ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Glycogen Synthase Kinase 3 / genetics ; Glycogen Synthase Kinase 3 beta ; Heterografts ; Humans ; Immunohistochemistry ; Lung Neoplasms / genetics ; Lung Neoplasms / metabolism ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; Microscopy, Confocal ; Mitochondrial Proteins / genetics ; Neoplasm Metastasis ; Protein Binding ; Protein Phosphatase 2 / genetics ; Protein Phosphatase 2 / metabolism ; RNA Interference ; Signal Transduction ; Succinate Dehydrogenase / genetics ; Tumor Burden ; beta Catenin / genetics References: Clin Cancer Res. 2011 Jan 15;17(2):247-54. (PMID: 21224366) ; Hepatology. 2009 Nov;50(5):1464-74. (PMID: 19821482) ; Science. 2009 Aug 28;325(5944):1139-42. (PMID: 19628817) ; PLoS One. 2011;6(10):e27053. (PMID: 22046442) ; Nature. 2012 Mar 18;483(7391):613-7. (PMID: 22425996) ; J Biol Chem. 2011 May 6;286(18):16218-28. (PMID: 21454711) ; Oncogene. 2011 Mar 24;30(12):1436-48. (PMID: 21057535) ; Cancer Cell. 2009 Sep 8;16(3):180-2. (PMID: 19732718) ; Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20900-5. (PMID: 19106302) ; Lung Cancer. 2013 Jan;79(1):54-8. (PMID: 23131495) ; Lung Cancer. 2012 Nov;78(2):161-6. (PMID: 22959241) ; Lung Cancer. 2013 Jan;79(1):1-7. (PMID: 23137549) ; FASEB J. 2005 Jun;19(8):1048-50. (PMID: 15788447) ; BMC Cancer. 2010 Feb 23;10:58. (PMID: 20178594) ; J Biol Chem. 2012 May 18;287(21):17746-17753. (PMID: 22457351) ; Oncogene. 2010 Oct 21;29(42):5741-54. (PMID: 20697346) ; Clin Cancer Res. 2012 Nov 15;18(22):6356-63. (PMID: 23014530) ; Science. 2012 Jan 20;335(6066):282-3. (PMID: 22267789) ; Gut. 2012 May;61(5):714-24. (PMID: 21873734) ; Oncogene. 2011 Mar 24;30(12):1449-59. (PMID: 21102519) ; Mol Cell Biochem. 2011 Mar;349(1-2):33-40. (PMID: 21116689) ; J Immunol. 2011 Dec 15;187(12):6539-49. (PMID: 22095718) ; Cancer Res. 2011 Feb 15;71(4):1235-43. (PMID: 21159661) ; Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15858-63. (PMID: 21911394) ; Endocrine. 2010 Dec;38(3):397-401. (PMID: 20972721) ; Hepatology. 2009 May;49(5):1515-24. (PMID: 19205031) ; J Appl Physiol (1985). 2011 Apr;110(4):892-900. (PMID: 21193562) Contributed Indexing: Keywords: Biomarkers; E-cadherin; EMT; Lung Cancer; Metastasis; Mitochondrial Protein; SDH5 Substance Nomenclature: 0 (Mitochondrial Proteins) ; 0 (SDHAF2 protein, human) ; 0 (beta Catenin) ; EC 1.3.99.1 (Succinate Dehydrogenase) ; EC 2.7.11.1 (GSK3B protein, human) ; EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) ; EC 2.7.11.1 (Gsk3b protein, mouse) ; EC 2.7.11.26 (Glycogen Synthase Kinase 3) ; EC 3.1.3.16 (Protein Phosphatase 2) Entry Date(s): Date Created: 20130829 Date Completed: 20131211 Latest Revision: 20211021 Update Code: 20240513 PubMed Central ID: PMC3795294

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Succinate dehydrogenase 5 (SDH5) regulates glycogen synthase kinase 3β-β-catenin-mediated lung cancer metastasis.