Regulation of Wnt / B-catenin signaling by small molecule compounds (WP3664)

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]
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Authors

AAR&Co, Lindarieswijk, Khanspers, DeSl, Mkutmon, MaintBot, Melodyner, and Eweitz

Cited In

Organism

Homo sapiens

Communities

CPTAC

Annotations

Disease Ontology: gastrointestinal carcinoma

Pathway Ontology: altered Wnt signaling pathway growth factor signaling pathway

Participants

Label Type Compact Identifier
iCRT14 Metabolite pubchem.compound:5967294
NSC668036 Metabolite chemspider:338019
AXIN1 GeneProduct ensembl:ENSG00000103126
PRK222-815 Metabolite None
FZD8 GeneProduct ensembl:ENSG00000177283
PRK118-744 Metabolite None
LEF1 GeneProduct ensembl:ENSG00000138795
IWP-2 Metabolite pubchem.compound:2155128
DKK3 GeneProduct ensembl:ENSG00000050165
NC043 Metabolite cas:1053172-87-4
iCRT5 Metabolite pubchem.compound:71749442
SFRP4 GeneProduct ensembl:ENSG00000106483
CGP049090 Metabolite chebi:3556
Retinoids Metabolite chebi:26537
XAV939 Metabolite chebi:62878
FZD7 GeneProduct ensembl:ENSG00000155760
DVL2 GeneProduct ensembl:ENSG00000004975
LRP GeneProduct ensembl:ENSG00000123384
Pyrvinium Metabolite chebi:8687
Glucocorticoids Metabolite chebi:24261
PRK118-310 Metabolite None
MBOAT GeneProduct ensembl:ENSG00000172197
1a,25-(OH)2D3 Metabolite pubchem.compound:5280453
ICG-001 Metabolite pubchem.compound:11238147
FZD GeneProduct hgnc.symbol:FZD1
TNKS GeneProduct ensembl:ENSG00000173273
PRK115-584 Metabolite None
GSK3B GeneProduct ensembl:ENSG00000082701
iCRT3 Metabolite pubchem.compound:6622273
CK1e GeneProduct uniprot:Q5R2U3
WNT GeneProduct ensembl:ENSG00000125084
IC261 Metabolite chebi:92168
APC GeneProduct ensembl:ENSG00000134982
TCF4 GeneProduct ensembl:ENSG00000196628
CK1a GeneProduct ensembl:ENSG00000113712
CTNNB1 GeneProduct ensembl:ENSG00000168036
WNT GeneProduct ensembl:ENSG00000125084
CTNNB1 GeneProduct ensembl:ENSG00000168036

References

  1. White BD, Chien AJ, Dawson DW. Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers. Gastroenterology. 2012 Feb;142(2):219–32. PubMed Europe PMC Scholia