PMID- 25527973 OWN - NLM STAT- MEDLINE DCOM- 20150921 LR - 20181113 IS - 1643-3750 (Electronic) IS - 1234-1010 (Print) IS - 1234-1010 (Linking) VI - 20 DP - 2014 Dec 21 TI - NF-kappaB signaling pathway confers neuroblastoma cells migration and invasion ability via the regulation of CXCR4. PG - 2746-52 LID - 10.12659/MSM.892597 [doi] AB - BACKGROUND: Accumulating evidence implicates the transcription factor NF-kappaB 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-kappaB signaling pathway in the regulation of CXC chemokine receptor-4 (CXCR4) in neuroblastoma metastasis. MATERIAL AND METHODS: NF-kappaB, CXCR4 mRNA and protein expression were measured by RT-PCR, and Western blot. Tumor necrosis factor-alpha (TNF-alpha) was used to induce the upregulation of NF-kappaB and CXCR4. The knockdown of NF-kappaB and CXCR4 was achieved by PDTC. Transwell assay was used to investigate the role of NF-kappaB (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-kappaB signaling pathway. RESULTS: Over-expression of NF-kappaB (p65) promoted tumor migration and invasion through the upregulation of CXCR4; however, knockdown of NF-kappaB(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-kappaB (p65). CONCLUSIONS: Our studies reveal critical roles for the NF-kappaB signaling pathway in neuroblastoma migration and invasion. The mechanism may be through up-regulation of CXCR4, mediated by the NF-kappaB signaling pathways. Targeting NF-kappaB signalling pathways and ultimately CXCR4 could be a strategy in neuroblastoma therapy. FAU - Zhi, Yunlai AU - Zhi Y AD - Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland). FAU - Duan, Yuhe AU - Duan Y AD - Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland). FAU - Zhou, Xianjun AU - Zhou X AD - Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland). FAU - Yin, Xiaofeng AU - Yin X AD - Department of Neurosurgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China (mainland). FAU - Guan, Ge AU - Guan G AD - Department of Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland). FAU - Zhang, Hong AU - Zhang H AD - Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland). FAU - Dong, Qian AU - Dong Q AD - Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland). FAU - Yang, Kun AU - Yang K AD - Department of Central Laboratory, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland). LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141221 PL - United States TA - Med Sci Monit JT - Medical science monitor : international medical journal of experimental and clinical research JID - 9609063 RN - 0 (Chemokine CXCL12) RN - 0 (NF-kappa B) RN - 0 (Receptors, CXCR4) SB - IM MH - Brain Neoplasms/metabolism/*pathology MH - Cell Line, Tumor MH - *Cell Movement/drug effects MH - Chemokine CXCL12/pharmacology MH - Coculture Techniques MH - Humans MH - Macrophages/drug effects/metabolism MH - NF-kappa B/*metabolism MH - Neoplasm Invasiveness MH - Neuroblastoma/metabolism/*pathology MH - Receptors, CXCR4/*metabolism MH - *Signal Transduction/drug effects MH - Up-Regulation PMC - PMC4280060 EDAT- 2014/12/22 06:00 MHDA- 2015/09/22 06:00 PMCR- 2014/12/21 CRDT- 2014/12/22 06:00 PHST- 2014/12/22 06:00 [entrez] PHST- 2014/12/22 06:00 [pubmed] PHST- 2015/09/22 06:00 [medline] PHST- 2014/12/21 00:00 [pmc-release] AID - 892597 [pii] AID - 10.12659/MSM.892597 [doi] PST - epublish SO - Med Sci Monit. 2014 Dec 21;20:2746-52. doi: 10.12659/MSM.892597.