Wnt inhibitory factor 1 (WIF1)

Wnt inhibitory factor 1 (WIF1) is a secreted protein that functions as a potent antagonist of Wnt signaling by binding directly to a broad subset of Wnt ligands in the extracellular space, thereby preventing their interaction with surface receptors of the Frizzled family[1][3][4]. WIF1 contains a unique N-terminal WIF domain with a lipid-binding pocket, followed by five epidermal growth factor (EGF)-like repeats involved in protein–protein or glycoprotein interactions[1][3][4]. WIF1 acts as a key regulator of canonical (β-catenin–dependent) and non-canonical Wnt signaling, and is involved in the regulation of embryonic development, tissue homeostasis, neurogenesis, stem cell maintenance, and regeneration[3][4]. In cancer, WIF1 functions as a tumor suppressor gene that is frequently downregulated or epigenetically silenced, which permits aberrant activation of Wnt pathways, promoting tumor progression, cell proliferation, and metastasis. Loss of WIF1 expression through promoter methylation has been frequently reported in a variety of malignancies, and restoration of its expression suppresses tumorigenic properties in cancer models[1][2][4]. Currently, no approved drugs directly target WIF1, though experimental approaches aim to modulate its expression or mimic its Wnt-inhibitory activity in oncology and regenerative medicine.

Other names

WIF1WIF-1UNQ191/PRO217wnt inhibitory factor 1

Binds and sequesters Wnt ligands, preventing their interaction with Frizzled receptors and downstream signaling. Negative feedback inhibition of Wnt/β-catenin pathway. Modulation of morphogen gradients in tissue development[1][2][3][4]