Regulation of Wnt / B-catenin signaling by small molecule compounds

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]

Wnt/B-catenin通路始于MBOAT激活Wnt家族，使Wnt蛋白得以从细胞中转位并与FZD和LRP结合，形成复合物。该复合物激发B-catenin与TF/LEF复合物结合，从而调节细胞中的基因表达。该通路的调控发生在多个层面。Wnt信号可被DKK3、FZD7、SFRP4、FZD8、V3Nter以及Wnt抗体或抑制FZD且阻止FZD/LRP/Wnt复合物形成的FZD抗体所抑制。另一层面的调控涉及由XAV939、DVL、IC261和Pyrvinium调节的降解复合物（TNKS/AXIN/GSK3B/APC/CK1a/CK1e），该复合物催化B-catenin的分解，从而抑制其与TCF/LEF复合物的结合。包括视黄醇、糖皮质激素和ICG-001在内的多种物质可抑制TCF/LEF复合物，以阻止Wnt/B-catenin信号通路促进基因转录。该通路基于White等人的图4。该通路上的蛋白质具有通过[CPTAC检测平台](https://assays.cancer.gov/available_assays?wp_id=WP3664)提供的靶向检测方法。