Molecular regulation and pharmacological targeting of the β-catenin destruction complex

Br J Pharmacol. 2017 Dec;174(24):4575-4588. doi: 10.1111/bph.13922. Epub 2017 Aug 11.


The β-catenin destruction complex is a dynamic cytosolic multiprotein assembly that provides a key node in Wnt signalling regulation. The core components of the destruction complex comprise the scaffold proteins axin and adenomatous polyposis coli and the Ser/Thr kinases casein kinase 1 and glycogen synthase kinase 3. In unstimulated cells, the destruction complex efficiently drives degradation of the transcriptional coactivator β-catenin, thereby preventing the activation of the Wnt/β-catenin pathway. Mutational inactivation of the destruction complex is a major pathway in the pathogenesis of cancer. Here, we review recent insights in the regulation of the β-catenin destruction complex, including newly identified interaction interfaces, regulatory elements and post-translationally controlled mechanisms. In addition, we discuss how mutations in core destruction complex components deregulate Wnt signalling via distinct mechanisms and how these findings open up potential therapeutic approaches to restore destruction complex activity in cancer cells.

Linked articles: This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Axin Signaling Complex / antagonists & inhibitors*
  • Axin Signaling Complex / metabolism*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Wnt Signaling Pathway / drug effects


  • Antineoplastic Agents
  • Axin Signaling Complex