Prognostic significance of nuclear factor-kB p105/p50 in human melanoma and its role in cell migration

Transcriptional factor nuclear factor-kappa B (NF-kappa B) family has been shown to play an important role in tumor pathogenesis and serve as a potential target in cancer therapy. However, it is necessary to clarify the specific functions of NF-kappa B members, which would provide the basis for the selective blockade and reduction of therapeutic side effects resulting from unspecific inhibition of NF-kappa B members. In this study, we explored the role of NF-kappa B p105/p50 in melanoma pathogenesis in vitro and in vivo. We found that the expression of NF-kappa B p105/p50 significantly increased in dysplastic nevi, primary melanoma, and metastatic melanoma compared with normal nevi (P = 0.0004, chi(2) test). Furthermore, NF-kappa B p105/p50 nuclear staining increased with melanoma progression and strong NF-kappa B p105/p50 nuclear staining was inversely correlated with disease-specific 5-year survival of patients with tumor thickness > 2.0 min (P = 0.014, log-rank test). Multivariate Cox regression analysis revealed that nuclear expression of NF-kappa B p105/p50 is an independent prognostic factor in this subgroup. Moreover, we found that upregulation of NF-kappa B p50 enhanced melanoma cell migration, whereas small interfering RNA knockdown inhibited cell migration. In addition, overexpression of NF-kappa B p50 induced RhoA activity and Rock-mediated formation of stress fiber in melanoma cells. Taken together, our data indicate that NF-kappa B p105/p50 may be an important marker for human melanoma progression and prognosis as well as a potentially selective therapeutic target.