Wnt

Wnt is a family of secreted signaling proteins that regulate cell fate, proliferation, and migration during embryonic development and in adult tissues. The name derives from the Drosophila gene Wingless (Wg) and the mouse int-1 gene. Wnts are lipid-modified glycoproteins that require the acyltransferase PORCN for secretion and activity, often trafficked with Wntless (WLS). They initiate signaling by binding Frizzled receptors, with co-receptors such as LRP5/6 participating in canonical signaling or engaging non-canonical routes.

Canonical Wnt signaling stabilizes β-catenin by inhibiting a destruction complex containing AXIN, APC, and GSK3β. Stabilized β-catenin accumulates in the nucleus and partners with TCF/LEF transcription factors to regulate target genes such as MYC, CCND1, and AXIN2. Non-canonical branches are β-catenin-independent and govern processes including planar cell polarity and calcium signaling through pathways involving RhoA, JNK, and PKC.

Wnt signaling is tightly regulated by secreted antagonists such as DKKs and SFRPs, and by cellular context. Dysregulation is linked to developmental disorders and cancer; for example, mutations that activate canonical signaling or disrupt the destruction complex promote tumorigenesis, notably colorectal cancer with APC mutations. Outside development, Wnt pathways influence stem cell maintenance, tissue regeneration, and neural and metabolic processes.

Historically, the name Wnt reflects Wingless and int-1; discovery and characterization of Wnt signaling expanded through the 1980s and 1990s. Wnts are secreted, palmitoylated proteins signaling through Frizzled receptors, with outcomes shaped by receptor/co-receptor composition and cellular context.