title: Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism.
abstract: Despite advances in basic and clinical research, metastasis remains the leading cause of death in breast cancer patients. Genetic abnormalities in mitochondria, including mutations affecting complex I and oxidative phosphorylation, are found in breast cancers and might facilitate metastasis. Genes encoding complex I components have significant breast cancer prognostic value. In this study, we used quantitative proteomic analyses to compare a highly metastatic cancer cell line and a parental breast cancer cell line; and observed that NDUFB9, an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I), was down-regulated in highly metastatic breast cancer cells. Furthermore, we demonstrated that loss of NDUFB9 promotes MDA-MB-231 cells proliferation, migration, and invasion because of elevated levels of mtROS, disturbance of the NAD+/NADH balance, and depletion of mtDNA. We also showed that, the Akt/mTOR/p70S6K signaling pathway and EMT might be involved in this mechanism. Thus, our findings contribute novel data to support the hypothesis that misregulation of mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, suggesting that complex I deficiency is a potential and important biomarker for further basic research or clinical application.
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
authors.forename: Liang-Dong
authors.initials: LD
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
authors.forename: He-Fen
authors.initials: HF
authors.lastname: Sun
authors.affiliation: Department of Radiotherapy, Lishui Central Hospital, Zhejiang, 323000, China.
authors.forename: Xue-Xiao
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Gao
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Jiang
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000235:genetics; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014407:Tumor Cells, Cultured
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D009245:NADH Dehydrogenase; C118906:NDUFB9 protein, human