FZD6 is a key gene that controls tissue polarity during development. Increasing evidence suggests that it also plays active roles in various cancers. In this study, we show that FZD6 is overexpressed in multiple melanoma cell lines and human samples. Knockdown or knockout of FZD6 does not affect cell proliferation but significantly reduces the invasive ability of melanoma cells. In addition, we have found that knockout of Fzd6 dramatically reduces lung metastasis in the Pten/BRaf mouse model of melanoma. Mechanistic studies in vitro and in vivo reveal a surprising involvement of canonical Wnt signaling and epithelial‒mesenchymal pathway in the FZD6-mediated invasive phenotype. Together, our study supports a promoter role of FZD6 in melanoma progression.
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