title: FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and contributes to nasopharyngeal cell proliferation, and metastasis via osteopontin/CD44 pathway.
abstract: BACKGROUND
  Nasopharyngeal carcinoma (NPC) is well-known for its highly metastatic characteristics, but little is known of its molecular mechanisms. New biomarkers that predict clinical outcome, in particular the ability of the primary tumor to develop metastatic tumors are urgently needed. The aim of this study is to investigate the role of FLJ10540 in human NPC development.
  
  
  METHODS
  A bioinformatics approach was used to explore the potentially important regulatory genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for this study. Two co-expression strategies from NPC microarray were employed to identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR, immunoblotting, and immunohistochemistry analysis were used to investigate the mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by stable transfection to further elucidate the molecular mechanisms of FLJ10540-elicited cell growth and metastasis under osteopontin stimulation.
  
  
  RESULTS
  We found that osteopontin expression exhibited a positive correlation with FLJ10540 in NPC microarray. We also demonstrated comprehensively that FLJ10540 and osteopontin were not only overexpressed in NPC specimens, but also significantly correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5-year survival rate, respectively. Stimulation of NPC parental cells with osteopontin results in an increase in FLJ10540 mRNA and protein expressions. Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin, exhibited fast growth and increased metastasis as compared to vehicle control with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by siRNA results in the suppression of NPC cell growth and motility. Treatment with anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell growth and motility in osteopontin stimulated-NPC cells.
  
  
  CONCLUSIONS
  These findings suggest that FLJ10540 may be critical regulator of disease progression in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway.
authors.affiliation: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chang-Han
authors.initials: CH
authors.lastname: Chen
authors.forename: Li-Yen
authors.initials: LY
authors.lastname: Shiu
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Su
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
authors.forename: Shun-Chen
authors.initials: SC
authors.lastname: Huang
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Yin
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Wang
authors.forename: Hsin-Ting
authors.initials: HT
authors.lastname: Tsai
authors.forename: Fu-Min
authors.initials: FM
authors.lastname: Fang
authors.forename: Wan-Chu
authors.initials: WC
authors.lastname: Chuang
authors.forename: Hong-Chang
authors.initials: HC
authors.lastname: Kang
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Hwang
mesh_terms: D002277:Carcinoma; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D009305:Nasopharynx / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C505378:Cep55 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D053495:Osteopontin