An oncogenic hub: beta-catenin as a molecular target for cancer therapeutics

Handb Exp Pharmacol. 2008;(186):261-84. doi: 10.1007/978-3-540-72843-6_11.

Abstract

The Wnt/beta-catenin signaling pathway plays diverse roles in embryonic development and in maintenance of organs and tissues in adults. Activation of this signaling cascade inhibits degradation of the pivotal component beta-catenin, which in turn stimulates transcription of downstream target genes. Over the past two decades, intensive worldwide investigations have yielded considerable progress toward understanding the cellular and molecular mechanisms of Wnt signaling and its involvement in the pathogenesis of a range of human diseases. Remarkably, beta-catenin signaling is aberrantly activated in greater than 70% of colorectal cancers and to a lesser extent in other tumor types, promoting cancer cell proliferation, survival and migration. Accordingly, beta-catenin has gained recognition as an enticing molecular target for cancer therapeutics. Disruption of protein-protein interactions essential for beta-catenin activity holds immense promise for the development of novel anti-cancer drugs. In this review, we focus on the regulation of beta-catenin-dependent transcriptional activation and discuss potential therapeutic opportunities to block this signaling pathway in cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Nucleus / metabolism
  • Drug Delivery Systems*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Signal Transduction
  • Transcriptional Activation / physiology
  • Wnt Proteins / drug effects*
  • Wnt Proteins / metabolism
  • beta Catenin / drug effects*
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents
  • Wnt Proteins
  • beta Catenin