title: NF-κB signaling pathway confers neuroblastoma cells migration and invasion ability via the regulation of CXCR4.
abstract: BACKGROUND
  Accumulating evidence implicates the transcription factor NF-κB as a positive mediator of tumor metastasis, but the molecular mechanism(s) involved in this process remains largely unknown. In this study, we investigated the role of NF-κB signaling pathway in the regulation of CXC chemokine receptor-4 (CXCR4) in neuroblastoma metastasis.
  
  
  METHODS
  NF-κB, CXCR4 mRNA and protein expression were measured by RT-PCR, and Western blot. Tumor necrosis factor-α (TNF-α) was used to induce the upregulation of NF-κB and CXCR4. The knockdown of NF-κB and CXCR4 was achieved by PDTC. Transwell assay was used to investigate the role of NF-κB (P65) in neuroblastoma cell migration and invasion. An in vitro co-culture system was established to investigate the role of tumor microenvironment in regulation of the NF-κB signaling pathway.
  
  
  RESULTS
  Over-expression of NF-κB (p65) promoted tumor migration and invasion through the upregulation of CXCR4; however, knockdown of NF-κB(P65) inhibited tumor migration and invasion through blocking the expression of CXCR4. Consistently, in the co-culture system, the expression of CXCR4 was partly dependent on the expression of NF-κB (p65).
  
  
  CONCLUSIONS
  Our studies reveal critical roles for the NF-κB signaling pathway in neuroblastoma migration and invasion. The mechanism may be through up-regulation of CXCR4, mediated by the NF-κB signaling pathways. Targeting NF-κB signalling pathways and ultimately CXCR4 could be a strategy in neuroblastoma therapy.
authors.affiliation: Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Yunlai
authors.initials: Y
authors.lastname: Zhi
authors.affiliation: Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Yuhe
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Xianjun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Ge
authors.initials: G
authors.lastname: Guan
authors.affiliation: Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Central Laboratory, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology; D018920:Coculture Techniques; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D054377:Chemokine CXCL12; D016328:NF-kappa B; D019718:Receptors, CXCR4