21 December 2014 : Laboratory Research
NF-κB Signaling Pathway Confers Neuroblastoma Cells Migration and Invasion Ability via the Regulation of CXCR4
Yunlai ZhiB, Yuhe DuanC, Xianjun ZhouD, Xiaofeng YinE, Ge GuanF, Hong ZhangG, Qian DongA, Kun YangFDOI: 10.12659/MSM.892597
Med Sci Monit 2014; 20:2746-2752
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.
MATERIAL AND 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.
Keywords: Brain Neoplasms - pathology, Cell Movement - drug effects, Chemokine CXCL12 - pharmacology, Coculture Techniques, Macrophages - metabolism, Neuroblastoma - pathology, Receptors, CXCR4 - metabolism, Signal Transduction - drug effects
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