The Wnt signaling pathway plays an essential role in the control of cell proliferation, aberrant activation of this pathway is responsible for the development of several types of cancer.

The activity of Wnts is regulated by a variety of secreted extracellular proteins that interfere with the formation of the Wnt-receptor complexes. Wnt inhibitory factor 1 (WIF1) binds directly to Wnts and prevents their binding to Wnt receptors. The importance of this Wnt-antagonist in the control of cell proliferation may be illustrated by the fact that epigenetic silencing of the WIF1 gene is associated with aberrant activation of the Wnt-pathway in cancers, whereas restoration of its expression inhibits tumor progression.

The value of WIF1-based tumor therapies, however, is limited by the fact that WIF1 protein binds to the various human Wnts with similar affinity: therapies based on wild type WIF1 are not specific enough to permit the selective and efficient inhibition of the Wnt involved in the growth of the tumor. The aim of this cooperation is to produce WIF1 variants that bind to selected Wnts with higher affinity, making them more promising antitumor agents.

László Patthy, András Perczel

Result_May 2020