Frizzled-2 and Frizzled-5 (FZD2/FZD5)

Frizzled-2 (FZD2) and Frizzled-5 (FZD5) are members of the Frizzled family of seven-transmembrane domain receptors that serve as primary receptors for Wnt signaling proteins (UniProt P41597, Q13467). These receptors play critical roles in embryonic development, cell fate determination, and the maintenance of adult tissue homeostasis through both canonical (beta-catenin dependent) and non-canonical signaling pathways (PubMed: 23918387). In many cancers, FZD2 and FZD5 are overexpressed, driving tumor growth, epithelial-mesenchymal transition (EMT), and the maintenance of cancer stem cells (PubMed: 25231400). Therapeutic strategies targeting these receptors often involve monoclonal antibodies, such as Vantictumab, which bind to the conserved cysteine-rich domain (CRD) to block Wnt ligand interaction (PubMed: 25605860). While showing promise in oncology, targeting these receptors presents challenges due to their essential role in normal physiology, particularly in bone metabolism, leading to side effects like decreased bone density (PubMed: 27551071).

Other names

Frizzled class receptor 2Frizzled class receptor 5Frizzled-2Frizzled-5FZD2FZD5Wnt receptor

Antagonism of the Wnt signaling pathway by binding to the extracellular cysteine-rich domain (CRD) of Frizzled receptors, thereby preventing the binding of Wnt ligands and inhibiting downstream beta-catenin stabilization and gene transcription.