Genomic insights into WNT/β-catenin signaling

Abstract

The canonical WNT pathway regulates the stability of the proto-oncogene β-catenin and is aberrantly activated in many cancer types. Studies in a wide range of experimental models confirm that β-catenin activity is required for tumor initiation in cancers where this pathway is deregulated. However, to date this pathway has proven to be challenging to target therapeutically. Moreover, several lines of evidence suggest that other components and regulators of β-catenin exist. Here we will describe recent structural and functional studies describing genomic alterations and new regulators of β-catenin that lead to aberrant activation of the WNT/β-catenin pathway. These findings provide new insights into the biology of WNT/β-catenin signaling and suggest potential therapeutic opportunities.

Keywords: WNT; YAP1; cancer; synthetic lethality; β-catenin.

Figure 1

Multiple pathways regulate β-catenin signaling. In normal homeostasis, the destruction complex regulates β-catenin stability (top). Mutations in components of the destruction complex lead to stabilization of β-catenin and activation of various context-dependent transcriptional complexes.