Wnt signaling from membrane to nucleus: β-catenin caught in a loop.

β-catenin is the central nuclear effector of the Wnt signaling pathway, and regulates other cellular processes including cell adhesion. Wnt stimulation of cells culminates in the nuclear translocation of β-catenin and transcriptional activation of target genes that function during both normal and malignant development. Constitutive activation of the Wnt pathway leads to inappropriate nuclear accumulation of β-catenin and gene transactivation, an important step in cancer progression. This has generated interest in the mechanisms regulating β-catenin nuclear accumulation and retention. Here we discuss recent advances in understanding feedback loops that trap β-catenin in the nucleus and provide potential insights into Wnt signaling and the development of anti-cancer drugs.