WNT3A
WNT3A is a secreted Wnt ligand: a signaling protein that binds Frizzled receptors on neighboring cells and activates the canonical Wnt pathway, whose central effector is β-catenin.
Function
WNT3A is lipid-modified (palmitoleoylated by PORCN), which both confines it to short-range signaling and is required for its secretion by Wntless. Bound to Frizzled and LRP5/6 at the receiving cell’s membrane, it disables the β-catenin destruction complex, and Wnt target genes turn on. WNT3A maintains stem-cell compartments - intestinal crypts, hematopoietic stem cells - and patterns tissues during development, where Wnt gradients are among the morphogen systems that organize the body plan.
In cancer
Overproduction of Wnt ligands is one route to pathway activation in tumors that keep their APC and CTNNB1 genes intact - pancreatic, breast, and lung cancers secrete Wnt ligands to sustain their own stem-like compartments and their stroma. WNT3A in the tumor microenvironment also acts on macrophages and fibroblasts, recruiting them into a tumor-supporting state. Pharmacological Wnt inhibition has been limited by the pathway’s role in the gut, where blocking it destroys the intestinal epithelium.
Notes
- Human gene symbol: WNT3A; UniProt P56704; 352 amino acids (precursor); Wnt family, 19 members in mammals.
- The name joins “Wingless” (the Drosophila gene) and “Int-1” (the mouse integration-site oncogene) - the same gene found twice.