Wnt-1 protein (WNT1)

Wnt-1 protein is a highly conserved, secreted glycoprotein belonging to the Wnt family of morphogens. It acts as a canonical Wnt ligand that binds the Frizzled and LRP5/6 receptors on the cell membrane, activating the Wnt/β-catenin signaling pathway. This pathway regulates cell fate, proliferation, differentiation, and migration during embryogenesis and in adult tissue homeostasis. WNT1 is involved in the formation and proliferation of neural progenitor cells, especially in the midbrain and hindbrain. Mutations lead to bone fragility syndromes, while overexpression is linked to tumorigenesis and poor prognosis in various cancers. Its complex folding, lipidation, and hydrophobic nature pose drug development challenges, but make it a crucial target and biomarker for several diseases.

Other names

wingless (Drosophila)INT1 (mouse)WNT1 proto-oncogene

Inhibition of WNT1-Frizzled binding and/or LRP5/6 recruitment blocks canonical Wnt/β-catenin signaling, which subsequently reduces β-catenin-mediated transcription of oncogenic and developmental target genes (e.g., c-Myc, cyclin D1). Inhibition of secretion and lipidation interferes with WNT1 function.