Figure 2. Wnt5A Signaling in Melanoma Metastasis.
Wnt5A binds to ROR2, perhaps via Frizzled, and is internalized via clathrin (CLTC), activating Ca2+ and PKC signaling which increases mRNA stabilization of Wnt5A and its increased secretion. Secreted Wnt5A is sequestered to the surface of the cell by HSPGs, and re-presented to its receptor, resulting in a positive feedback loop, with multiple downstream effects that promote a metastatic phenotype, including an EMT, upregulation of CD44, loss of Kiss-1, downregulation of melanogenic antigens, and cytoskeletal changes. See text for details.
