SOX4 promotes melanoma cell migration and invasion though the activation of the NF-κB signaling pathway.

Abstract

SOX4 has been reported to be abnormally expressed in many types of cancer, including melanoma. However, its role in cell proliferation and metastasis remains controversial. In this study, SOX4 was downregulated or overexpressed in A375, A2058 and A875 melanoma cells by siRNA or lentivirus transfection, respectively. Cell metastasis was observed by Transwell assay. In an aim to elucidate the underlying mechanisms, we determined the expression of nuclear factor-κB (NF-κB) by real-time PCR assay and western blot analysis. Our data indicated that SOX4 knockdown inhibited melanoma cell migration and invasion. In the melanoma cells in which SOX4 was downregulated, the expression levels of NF-κB/p65, matrix metalloproteinase (MMP)2 and MMP9 were suppressed at both the mRNA and protein levels. Conversely, the overexpres-sion of SOX4 promoted melanoma cell migration and invasion. In the melanoma cells in which SOX4 was overexpressed, the expression levels of NF-κB/p65, MMP2 and MMP9 were increased at both the mRNA and protein level. On the whole, our findings indicate that SOX4 promotes melanoma cell migration and invasion through the activation of the NF-κB/p65 signaling pathway. Thus, SOX4 may prove to be a potential therapeutic target for the treatment of melanoma.