title: Suppression of mitochondrial complex I influences cell metastatic properties.
abstract: Despite the fact that mitochondrial dysfunction has an important role in tumorigenesis and metastasis, the underlying mechanism remains to be elucidated. Mitochondrial Complex I (NADH:ubiquinone oxidoreductase) is the first and the largest protein complex of the mitochondrial electron-transport chain (ETC),which has an essential role in maintaining mitochondrial function and integrity. In this study, we separately knocked down two subunits of mitochondrial complex I, GRIM-19 or NDUFS3, and investigated their effects on metastatic behaviors and explored the possible mechanisms. Our data showed that stable down-modulation of GRIM-19 or NDUFS3 decreased complex I activity and reactive oxygen species (ROS) production; led to enhanced cell adhesion, migration, invasion, and spheroid formation; and influenced the expressions of extracellular matrix (ECM) molecules and its related proteins. We also observed that the expressions of GRIM-19, NDUFS3, and ECM elements were correlated with invasive capabilities of breast cancer cell lines. These results suggest that inhibition of complex I affects metastatic properties of cancer cells, and mitochondrial ROS might play a crucial role in these processes by regulating ECM.
authors: Central Laboratory, Wuhan Medical and Healthcare Center for Women and Children, Hubei, China. hxljm07@hotmail.com
authors: Xuelian
authors: X
authors: He
authors: Aifen
authors: A
authors: Zhou
authors: Hao
authors: H
authors: Lu
authors: Yong
authors: Y
authors: Chen
authors: Guochang
authors: G
authors: Huang
authors: Xin
authors: X
authors: Yue
authors: Peiwei
authors: P
authors: Zhao
authors: Yanxiang
authors: Y
authors: Wu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C050361:CDH2 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D005353:Fibronectins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016023:Integrins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C472512:NDUFS3 protein, human
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