Frizzled-8 receptor (FZD8)

Frizzled-8 receptor (*FZD8*) is a seven-transmembrane G protein-coupled receptor and a key member of the Wnt receptor family. Its extracellular N-terminal cysteine-rich domain (CRD) directly binds Wnt ligands, mediating both canonical (β-catenin dependent) and non-canonical Wnt signaling pathways that regulate development, cell proliferation, and cell fate decisions[1][2][4][7][8]. The CRD recognizes lipid-modified Wnt proteins—with the palmitoleic acid group of Wnt ligands inserting into a hydrophobic groove in the domain—and participates in binding specificity, often in partnership with LRP5/6 co-receptors[5]. FZD8 is implicated in several cancers, particularly by integrating Wnt-11 and TGF-β signals to promote epithelial-mesenchymal transition, invasion, and metastasis in prostate cancer; as such, it is considered a promising therapeutic target[6][7]. While there are small molecules identified that block the Wnt–Frizzled-8 CRD interaction, there are no approved drugs that specifically act through FZD8 as of now[3].

Other names

Frizzled-8Fz-8FZD8Frizzled class receptor 8Frizzled, Drosophila, homolog of, 8

Inhibition of Wnt binding to Frizzled-8 extracellular CRD impedes downstream canonical (β-catenin dependent) and non-canonical Wnt signaling Porcupine inhibitors block Wnt ligand palmitoleoylation, thus preventing Frizzled activation[3][2]