Wnt–β-catenin signaling pathway (Wnt/β-catenin pathway)

The Wnt–β-catenin signaling pathway (canonical Wnt pathway) is a highly conserved signal transduction cascade that regulates a broad range of developmental and homeostatic processes. Canonical activation begins with Wnt protein binding to Frizzled and LRP5/6 cell-surface co-receptors, inhibiting a cytoplasmic destruction complex (Axin, APC, GSK3, CK1), allowing β-catenin to accumulate and translocate into the nucleus. Here, β-catenin acts as a transcriptional coactivator for TCF/LEF transcription factors, regulating genes involved in cell proliferation, differentiation, migration, and stem cell maintenance[1][3][5][7]. Dysregulation of this pathway is strongly implicated in cancer, bone diseases, neurodegeneration, and fibrotic conditions, making it a critical therapeutic target but one with substantial safety concerns due to its fundamental roles in tissue homeostasis and regeneration[2][4][6].

Other names

Canonical Wnt pathwayWnt/β-catenin pathwayWnt–β-catenin signal transduction

Inhibition of Wnt ligand secretion (PORCN inhibitors block posttranslational acylation of Wnt ligands)[2] Disruption of β-catenin/TCF transcriptional activity (antagonists)[6] Inhibition of v-ATPase to block Wnt pathway signaling downstream or independent of APC mutations[2] Stabilization of β-catenin by GSK-3β inhibition[4] Activating or blocking receptor–ligand interactions (e.g., anti-Frizzled antibodies, Wnt mimics)[4]