The Wnt/B-catenin pathway begins with Wnt family activation by MBOAT that allows Wnt proteins to translocate out of a cell and bind to FZD and LRP to form a complex. This complex stimulates B-catenin to bind to the TF/LEF complex to regulate gene expression in the cell. Regulation of this pathway takes place at different levels. The Wnt signaling can be inhibited by DKK3, FZD7, SFRP4, FZD8, V3Nter, and Wnt antibodies or FZD antibodies that inhibit FZD and do not allow formation of FZD/LRP/Wnt complex. Another level of regulation is the destruction complex (TNKS/AXIN/GSK3B/APC/CK1a/CK1e) that is regulated by XAV939, DVL, IC261, and Pyrvinium to catalyze the breakdown of B-catenin, inhibiting its binding to the TCF/LEF complex. Several substances including retinoids, glucocorticoids, and ICG-001 inhibit the TCF/LEF complex to stop Wnt/B-catenin signaling pathways from promoting gene transcription. This pathway is based on figure 4 from White et al.
Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3664 CPTAC Assay Portal]c93Identifier Not FoundIdentifier Not FoundLRP Not SpecifiedIdentifier Not FoundMBOAT FamilyFZD Not SpecifiedIdentifier Not FoundWnt Not SpecifiedWnt Not Specifiedgastrointestinal carcinomaDOID:0050922Human Disease Ontologyaltered Wnt signaling pathwayPW:0000598Pathway Ontologygrowth factor signaling pathwayPW:0000168Pathway Ontology22155636PubMedDysregulation of Wnt/β-catenin signaling in gastrointestinal cancers.Gastroenterology2012White BDChien AJDawson DW