Wnt/β-catenin
Definition
The Wnt/β-catenin pathway is a highly conserved signal transduction cascade that regulates cell proliferation, differentiation, and stem cell maintenance. When Wnt ligands bind to Frizzled receptors and LRP5/6 co-receptors, they inhibit the β-catenin destruction complex (comprising APC, Axin, GSK3β, and CK1). This stabilizes cytoplasmic β-catenin, allowing it to translocate to the nucleus where it interacts with TCF/LEF transcription factors to activate target gene expression. Dysregulation of this pathway is implicated in numerous cancers, developmental disorders, and degenerative diseases. The pathway's complexity involves multiple feedback loops, crosstalk with other signaling networks, and context-dependent outcomes that vary across tissue types and developmental stages.
Visualize Wnt/β-catenin in Nodes Bio
Researchers can map the Wnt/β-catenin pathway as a multi-layered network showing ligand-receptor interactions, cytoplasmic signaling cascades, and downstream transcriptional targets. Nodes Bio enables visualization of pathway crosstalk with other signaling networks (Notch, Hedgehog, TGF-β), identification of regulatory feedback loops, and integration of mutation data to understand how pathway perturbations drive disease phenotypes in specific cancer types or developmental contexts.
Visualization Ideas:
- Canonical vs non-canonical Wnt pathway comparison networks
- β-catenin protein interaction networks with destruction complex components and transcriptional co-factors
- Multi-omics integration showing Wnt pathway gene expression, protein levels, and mutation status across cancer subtypes
Example Use Case
A colorectal cancer research team investigating resistance to targeted therapies discovers that APC mutations lead to constitutive Wnt pathway activation. Using network analysis, they map how β-catenin accumulation triggers expression of genes like MYC and CCND1, while simultaneously identifying compensatory pathway activation through EGFR signaling. By visualizing protein-protein interactions between pathway components and overlaying patient mutation data, they identify combination therapy targets that simultaneously inhibit both Wnt and EGFR signaling to overcome resistance mechanisms.