Beschreibung:
<jats:title>Summary</jats:title><jats:p>The sry‐related high‐mobility box (<jats:styled-content style="fixed-case">SOX</jats:styled-content>)‐2 protein has recently been proven to play a significant role in progression, metastasis, and clinical prognosis spanning several cancer types. Research on the role of <jats:styled-content style="fixed-case">SOX</jats:styled-content>2 in melanoma is limited and currently little is known about the mechanistic function of this gene in this context. Here, we observed high expression of <jats:styled-content style="fixed-case">SOX</jats:styled-content>2 in both human melanoma cell lines and primary melanomas in contrast to melanocytic nevi. This overexpression in melanoma can, in part, be explained by extra gene copy numbers of <jats:styled-content style="fixed-case">SOX</jats:styled-content>2 in primary samples. Interestingly, we were able to induce <jats:styled-content style="fixed-case">SOX</jats:styled-content>2 expression, mediated by <jats:styled-content style="fixed-case">SOX</jats:styled-content>4, <jats:italic>via </jats:italic><jats:styled-content style="fixed-case">TGF</jats:styled-content>‐<jats:italic>β</jats:italic>1 stimulation in a time‐dependent manner. Moreover, the knockdown of <jats:styled-content style="fixed-case">SOX</jats:styled-content>2 impaired <jats:styled-content style="fixed-case">TGF</jats:styled-content>‐<jats:italic>β</jats:italic>‐induced invasiveness. This phenotype switch can be explained by <jats:styled-content style="fixed-case">SOX</jats:styled-content>2‐mediated cross talk between <jats:styled-content style="fixed-case">TGF</jats:styled-content>‐<jats:italic>β</jats:italic> and non‐canonical Wnt signaling. Thus, we propose that <jats:styled-content style="fixed-case">SOX</jats:styled-content>2 is involved in the critical <jats:styled-content style="fixed-case">TGF</jats:styled-content>‐<jats:italic>β</jats:italic> signaling pathway, which has been shown to correlate with melanoma aggressiveness and metastasis. In conclusion, we have identified a novel downstream factor of <jats:styled-content style="fixed-case">TGF</jats:styled-content>‐<jats:italic>β</jats:italic> signaling in melanoma, which may have further implications in the clinic.</jats:p>