title: Mitochondrial proteomics of nasopharyngeal carcinoma metastasis.
abstract: BACKGROUND
  Mitochondrial proteomic alterations of nasopharyngeal carcinoma metastasis remain unknown. Our purpose is to screen mitochondrial proteins for the elucidation of the molecular mechanisms of nasopharyngeal carcinoma metastasis and the discovery of metastasis-related biomarkers.
  
  
  METHODS
  Mitochondria were isolated from nasopharyngeal carcinoma metastatic (5-8F) and nonmetastatic (6-10B) cell lines, respectively. After characterization of isolated mitochondria, mitochondrial differentially expressed proteins (DEPs) were quantified by two-dimensional difference in-gel electrophoresis (2D-DIGE), and identified by peptide mass fingerprint (PMF) and tandem mass spectrometry (MS/MS). A functional enrichment analysis and a protein-protein interaction sub-network analysis for DEPs were carried out with bioinformatics. Furthermore, siRNAs transient transfections were used to suppress expressions of some up-regulated DEPs in metastatic cells (5-8F), followed by Transwell Migration assay.
  
  
  RESULTS
  Sixteen mitochondrial DEPs including PRDX3 and SOD2 were identified. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity. A protein-protein interaction sub-network of DEPs was generated with literature data. Ten mitochondrial DEPs including PRDX3, PRDX6, SOD2, ECH1, SERPINB5, COX5A, PDIA5, EIF5A, IDH3B, and PSMC4 were rationalized in the tumor-stroma co-evolution model that mitochondrial oxidative stress directly contributes to tumor metastasis.
  
  
  CONCLUSIONS
  Sixteen mitochondrial DEPs were identified with mass spectrometry and ten of them were rationalized in the tumor-stroma co-evolution model. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.forename: Xianquan
authors.initials: X
authors.lastname: Zhan
authors.forename: Maoyu
authors.initials: M
authors.lastname: Li
authors.forename: Guoqing
authors.initials: G
authors.lastname: Li
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.forename: Zhefeng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Meiying
authors.initials: M
authors.lastname: Shao
authors.forename: Fang
authors.initials: F
authors.lastname: Peng
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Zhuchu
authors.initials: Z
authors.lastname: Chen
mesh_terms: D015153:Blotting, Western; D002277:Carcinoma; D002452:Cell Count; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement; D006801:Humans; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009362:Neoplasm Metastasis; D010449:Peptide Mapping; D061105:Peroxiredoxin III / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D014162:Transfection; D057825:Two-Dimensional Difference Gel Electrophoresis; D015854:Up-Regulation
chemical_list: D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III