Targeting the interaction of ß-catenin and TCF/LEF transcription factors to inhibit oncogenic Wnt signaling.

The Wnt/ß-catenin signaling pathway is crucially involved in embryonic development, stem cell maintenance and tissue renewal. Hyperactivation of this pathway is associated with the development and progression of various types of cancers. The transcriptional coactivator ß-catenin represents a pivotal component of the pathway and its interaction with transcription factors of the TCF/LEF family is central to pathway activation. Inhibition of this crucial protein-protein interaction via direct targeting of ß-catenin is considered a promising strategy for the inactivation of oncogenic Wnt signaling. This review summarizes advances in the development of Wnt antagonists that have been shown to directly bind ß-catenin.