Rationale for targeting the Wnt signalling modulator Dickkopf-1 for oncology.

Abstract

Wnt signalling is a fundamental pathway involved in embryonic development and adult tissue homeostasis. Mutations in the pathway frequently lead to developmental defects and cancer. As such, therapeutic intervention of this pathway has generated tremendous interest. Dickkopf-1 (DKK1) is a secreted inhibitor of β-catenin-dependent Wnt signalling and was originally characterized as a tumour suppressor based on the prevailing view that Wnt signalling promotes cancer pathogenesis. However, DKK1 appears to increase tumour growth and metastasis in preclinical models and its elevated expression correlates with a poor prognosis in a range of cancers, indicating that DKK1 has more complex cellular and biological functions than originally appreciated. Here, we review current evidence for the cancer-promoting activity of DKK1 and recent insights into the effects of DKK1 on signalling pathways in both cancer and immune cells. We discuss the rationale and promise of targeting DKK1 for oncology.

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 http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.

• Authors: Michael H Kagey, Xi He
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 174 Issue 24 Pg. 4637-4650 (Dec 2017) ISSN: 1476-5381 [Electronic] England
• PMID: 28574171 (Publication Type: Journal Article, Review)
• Copyright: © 2017 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Chemical References

• DKK1 protein, human
• Dkk1 protein, mouse
• Intercellular Signaling Peptides and Proteins

Topics

• Animals
• Humans
• Intercellular Signaling Peptides and Proteins (metabolism)
• Neoplasms (drug therapy, metabolism)
• Wnt Signaling Pathway (drug effects)