Suppression of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma through IKKβ inhibition

We explored the role of the transcription factor, NF-kappa B, and its upstream kinase IKK beta in regulation of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). We showed that cisplatin-resistant HNSCC cells have a stronger ability to migrate and invade, as well as display higher IKK beta/NF-kappa B activity compared to their parental partners. Importantly, we found that knockdown of IKK beta, but not NF-kappa B, dramatically impaired cell migration and invasion in these cells. Consistent with this, the IKK beta inhibitor, CmpdA, also inhibited cell migration and invasion. Previous studies have already shown that N-Cadherin, an epithelial-mesenchymal transition (EMT) marker, and IL-6, a pro-inflammatory cytokine, play important roles in regulation of HNSCC migration, invasion, and metastasis. We found that cisplatin-resistant HNSCC expressed higher levels of N-Cadherin and IL-6, which were significantly inhibited by CmpdA. More importantly, we showed that CmpdA treatment dramatically abated cisplatin-resistant HNSCC cell metastasis to lungs in a mouse model. Our data demonstrated the crucial role of IKK beta in control of migration, invasion, and metastasis, and implicated that targeting IKK beta may be a potential therapy for cisplatin-resistant metastatic HNSCC.