title: ZNF488 Enhances the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Via the Wnt Signaling Pathway Involving Epithelial Mesenchymal Transition.
abstract: OBJECTIVE
  The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef.
  
  
  RESULTS
  ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/β-catenin signaling pathway.
  
  
  CONCLUSIONS
  Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/β-catenin pathway to induce EMT in NPC.
authors.affiliation: Jiangsu Cancer Hospital, Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zong
authors.affiliation: Jiangsu Cancer Hospital, Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Jiangsu Cancer Hospital, Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Guo
authors.affiliation: Jiangsu Cancer Hospital, Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Xu
authors.affiliation: Jiangsu Cancer Hospital, Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Zhi-Rui
authors.initials: ZR
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Man-Zhi
authors.initials: MZ
authors.lastname: Li
authors.affiliation: Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: Jiangsu Cancer Hospital, Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Jiangsu Cancer Hospital, Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D000066673:Cell Self Renewal; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D051822:T Cell Transcription Factor 1 / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051821:Lymphoid Enhancer-Binding Factor 1; D051822:T Cell Transcription Factor 1; D051176:beta Catenin
keywords: Carcinogenesis; Epithelial-mesenchymal transition; Invasion; Nasopharyngeal carcinoma; Wnt signaling pathway; ZNF488