betacateninTCF

Beta-catenin–TCF, often described as the beta-catenin/TCF complex, is the principal transcriptional effector of the canonical Wnt signaling pathway. It forms in the nucleus when beta-catenin, stabilized in response to Wnt signals, binds to TCF/LEF family transcription factors to regulate target gene expression.

In the absence of Wnt signals, beta-catenin is kept at low levels by the destruction complex, which includes APC, AXIN, GSK3β, and CK1 and promotes its phosphorylation and ubiquitin-mediated degradation. When Wnt ligands engage Frizzled and LRP5/6 receptors, the destruction complex is inhibited, allowing beta-catenin to accumulate and translocate to the nucleus. There, it binds TCF/LEF factors, displaces transcriptional repressors such as Groucho, and recruits co-activators like CBP/p300, BCL9, and Pygo to drive transcription of target genes such as MYC, CCND1, and AXIN2, among others. The exact gene set can vary by cell type and context.

Biological roles of the beta-catenin–TCF complex include regulation of cell proliferation, differentiation, and stem cell maintenance during development and tissue homeostasis. Dysregulated activation of this complex, through mutations in CTNNB1 (beta-catenin) or APC or other pathway components, is a common feature in several cancers, most prominently colorectal cancer, but also hepatocellular carcinoma and others. Because of its central role in growth signaling, beta-catenin–TCF is a target of research aimed at developing therapies that disrupt the interaction or downstream transcriptional activity while preserving normal tissue function.