Prognostic Significance of Sox4 Expression in Human Cutaneous Melanoma and Its Role in Cell Migration and Invasion

The Sox4 transcription factor is involved m various cellular processes such as embryonic development and differentiation Deregulated expression of Sox4 in several human cancers has been reported to date but its role in melanoma is unknown We explored the role of Sox4 in melanoma pathogenesis in vivo and in vitro Using tissue microarray we evaluated Sox4 expression in 180 melanocytic lesions and investigated its role in melanoma cell migration and invasion Sox4 expression was remarkably reduced in metastatic melanoma compared with dysplastic nev1 (P < 0 05) and primary melanoma (P < 0 01) This reduction was correlated with a poorer disease specific survival of melanoma patients (P = 0 039) Multivariate Cox regression analysis revealed that reduced Sox4 expression is an independent prognostic factor (P = 0 049) Knockdown of Sox4 enhanced melanoma cell invasion migration and stress fiber formation The increased migration and invasion on Sox4 knockdown depends on the presence of nuclear factor (NF) kappa B p50 and is abrogated when p50 is knocked down We further observed inhibition of NF kappa B p50 transcription by Sox4 in addition to a reverse pattern of expression of Sox4 and NF kappa B p50 in different stages of melanocytic lesions Our results suggest that Sox4 regulates melanoma cell migration and invasion in an NF kappa B p50 dependent manner and may serve as a prognostic marker and potential therapeutic target for human melanoma (Am J Pathol 2010 177 2741-2752 DOI 10 2353/ajpath 2010 100377)