Slug Expression during Melanoma Progression

Abstract

Slug (Snai2), a member of the Snail family of zinc finger transcription factors, plays a role in the epithelial-to-mesenchymal transformation (EMT) that occurs during melanocyte emigration from the neural crest. A role for Slug in the EMT-like loss of cell adhesion and increased cell motility exhibited during melanoma progression has also been proposed. Our immunohistochemical studies of melanoma arrays, however, revealed that Slug expression was actually higher in nevi than in primary or metastatic melanomas. Moreover, Slug expression in melanomas was not associated with decreased expression of E-cadherin, the canonical Slug target in EMT. Comparisons of endogenous Slug and E-cadherin expression in cultured normal human melanocytes and melanoma cell lines supported our immunohistochemical findings. Expression of exogenous Slug in melanocytes and melanoma cells in vitro, however, suppressed E-cadherin expression, enhanced N-cadherin expression, and stimulated cell migration and invasion. Interestingly, both in tumors and cultured cell lines, there was a clear relationship between expression of Slug and MITF, a transcription factor known to regulate Slug expression during development. Taken together, our findings suggest that Slug expression during melanomagenesis is highest early in the process and that persistent Slug expression is not required for melanoma progression. The precise role of Slug in melanomagenesis remains to be elucidated and may be related to its interactions with other drivers of EMT, such as Snail. (Am J Pathol 2012, 180:2479-2489; http://dx.doi.org/10.1016/j.ajpath.2012.02.014)