SDF-1α promotes invasion of head and neck squamous cell carcinoma by activating NF-κB

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.