Structure, function and disease relevance of Wnt inhibitory factor 1, a secreted protein controlling the Wnt and hedgehog pathways

Abstract

Wnts and Hedgehogs (Hh) are large, lipid-modified extracellular morphogens that play key roles in embryonic development and stem cell proliferation of Metazoa. Both morphogens signal through heptahelical Frizzled-type receptors of the G-Protein Coupled Receptor family and there are several other similarities that suggest a common evolutionary origin of the Hh and Wnt pathways. There is evidence that the secreted protein, Wnt inhibitory factor 1 (WIF1) modulates the activity of both Wnts and Hhs and may thus contribute to the intertwining of these pathways. In this article, we review the structure, evolution, molecular interactions and functions of WIF1 with major emphasis on its role in carcinogenesis.

Keywords:

• Cancer
• epigenetic silencing
• evolution
• hedgehog
• promoter hypermethylation
• Wnt
• Wnt inhibitory factor 1

Acknowledgments

We would like to thank Professor Laszlo Buday for his critical input into this article.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a grant of project no. FIEK_16-1-2016-0005 “Development of molecular biomarker research and service center”, with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the FIEK_16 funding scheme.