Down-regulation of FZD3 receptor suppresses growth and metastasis of human melanoma independently of canonical WNT signaling

Significance In malignant melanoma, one of the most aggressive cancers, the components of the WNT pathway are frequently deregulated and have been shown to drive self-renewal and metastatic progression of melanoma cells. Identifying tumorigenic properties of key members of the WNT signaling network in the pathogenesis of melanoma represents a pivotal task in the field and underlies successful design of targeted therapeutic approaches. In the present study, we characterized Frizzled 3 receptor (FZD3) as a critical factor underlying tumorigenic properties of aggressive human melanoma. Using in vivo and in vitro tumorigenic assays, combined with functional transcriptomics analysis of FZD3 knockdown in human patient-derived cells, we determined key signaling nodes regulated by FZD3 activity during malignant transformation.