Wntless Wnt transport mediator (WLS) (WLS)

Wntless Wnt transport mediator (WLS), also known as GPR177, is a highly conserved multipass transmembrane protein essential for the secretion of all Wnt signaling ligands. It functions as a dedicated cargo receptor that escorts lipidated Wnt proteins from the Golgi apparatus to the cell surface. In the context of pancreatic development, WLS-mediated Wnt secretion is critical for the expansion and compartmentalization of multipotent pancreatic progenitor cells. Dysregulation of WLS is frequently observed in various malignancies, particularly pancreatic ductal adenocarcinoma, where its overexpression drives aberrant canonical Wnt pathway activation and promotes tumor progression. Consequently, WLS is considered a significant therapeutic target, with research focusing on small molecule inhibitors and antibodies to block Wnt secretion and suppress oncogenic signaling. Its role in maintaining adult tissue homeostasis, however, poses challenges for therapeutic window and safety.

Other names

GPR177WntlessEviEvenness interruptedG protein-coupled receptor 177C1orf139MRP

Wntless (WLS/GPR177) acts as a specialized cargo receptor that binds to lipid-modified Wnt proteins in the endoplasmic reticulum and Golgi apparatus, transporting them to the plasma membrane for secretion. By facilitating the release of Wnt ligands, it enables the activation of the canonical Wnt/beta-catenin signaling pathway in receiving cells, such as pancreatic progenitor cells, which is essential for their expansion and subsequent differentiation during organogenesis.