Wnt5A (protein) and β-catenin-dependent Wnt signaling pathway (Wnt5A for the ligand, β-catenin pathway for the downstream signaling; no universal standard abbreviation for the combined "Wnt5A/β-catenin pathway")

Wnt5A is a member of the Wnt family of secreted glycoproteins that typically signals through non-canonical (β-catenin-independent) pathways, but it can also modulate the canonical Wnt/β-catenin pathway depending on cellular context and receptor expression. Wnt5A can either inhibit or activate β-catenin-dependent signaling, acting through receptors such as ROR2, Frizzleds (FZD4/5), and co-receptors like LRP5/6. Mechanistically, Wnt5A suppresses β-catenin signaling by promoting its degradation or enhancing alternative cascades (e.g., CaMKII), but in the presence of certain receptors, it may activate the canonical pathway. This context-sensitivity gives Wnt5A tumor suppressor or oncogenic roles depending on tissue type. Therapeutic targeting aims to restore normal Wnt5A signaling using mimetic peptides (Foxy-5) or modulate β-catenin stability. The pathway is intimately involved in development, differentiation, and cancer progression, making it a promising—but challenging—therapeutic target.

Other names

Wnt5AWnt-5aWNT5A-beta-catenin signalingNon-canonical Wnt signaling (for Wnt5A’s major pathway)Canonical Wnt pathway (for β-catenin axis)Wnt5A/β-catenin signaling axis

Inhibition of cell migration/invasion via Wnt5A mimetics Antagonism/activation of β-catenin signaling, depending on receptor and cellular context Modulation of Wnt/β-catenin pathway (stabilization or degradation of β-catenin by Wnt5A)