期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 29, 页码 19888-19894出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M710432200
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资金
- NIDCR NIH HHS [DE 13848, DE 15964] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007315] Funding Source: Medline
CXCL12/stromal cell-derived factor-1 alpha (SDF-1 alpha), a chemokine ligand for the G protein-coupled receptor CXCR4, plays an important role in the directed movement of cells. Many studies have documented the importance of CXCR4 in tumor progression and organ-specific metastasis. Recently, several studies have implicated a role for SDF-1 alpha in head and neck squamous cell carcinoma (HNSCC) metastasis, but currently there is little information about how SDF-1 alpha promotes HNSCC metastasis. In this report we show that the NF-kappa B signaling pathway is activated in response to SDF-1 alpha in HNSCC while primary and immortalized keratinocytes show no SDF-1 alpha-mediated NF-kappa B activity. We found that SDF-1 alpha-mediated NF-kappa B signaling is independent of phosphoinositide 3-kinase/Akt and ERK/MAPK pathways. We observed that SDF-1 alpha induces I kappa B alpha phosphorylation and degradation and the nuclear translocation of NF-kappa B in HNSCC cell lines, suggesting that SDF-1 alpha activates the classical NF-kappa B signaling pathway. Contrary to previous reports, SDF-1 alpha-induced NF-kappa B activation is not mediated by tumor necrosis factor alpha. Furthermore, blocking the NF-kappa B signaling pathway with an IKK beta inhibitor significantly reduces SDF-1 alpha-mediated HNSCC invasion. Taken together, our data suggest SDF-1 alpha/CXCR4 may promote HNSCC invasion and metastasis by activating NF-kappa B and that targeting NF-kappa B may provide therapeutic opportunities in preventing HNSCC metastasis mediated by SDF-1 alpha.
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