WNT (Wingless Int-1) 抑制因子

The Wnt family signaling pathways are crucial in regulating a wide array of developmental processes, including cell proliferation, differentiation, migration, and apoptosis. These pathways are categorized into two main types: the canonical (β-catenin-dependent) and the non-canonical (β-catenin-independent) pathways. In the canonical pathway, Wnt proteins bind to Frizzled receptors and LRP5/6 co-receptors, leading to stabilization and nuclear translocation of β-catenin, which activates Wnt-responsive genes. Non-canonical pathways, on the other hand, involve processes like planar cell polarity and calcium signaling, independent of β-catenin. Dysregulation of Wnt signaling is implicated in various diseases, including cancers, congenital defects, and degenerative diseases, highlighting its fundamental role in cell biology and pathology.

Targeting the Wnt family for disruption or inhibition involves strategies aimed at various components of the Wnt signaling pathways. Small molecule inhibitors, such as XAV-939, target the destruction complex in the canonical pathway, preventing β-catenin stabilization. Inhibitors like LGK-974 work by preventing the secretion of Wnt ligands, thus blocking Wnt signaling at an upstream level. For non-canonical pathways, inhibitors are designed to interfere with receptor-ligand interactions or downstream signaling components.