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Abstract. FZD7 receptor is considered as an emerging target for the treatment of Wnt-βcatenin related cancers. This transmembrane receptor is overexpressed in many cancer types like breast cancer and ovarian carcinoma, and so selective targeting of this receptor has a great therapeutic capacity. On the other hand, one of the mechanisms proposed for the anticancer effect of Atrial natriuretic peptide (ANP) that known as a heart hormone at first, is Wnt-βcatenin inhibition through an FZD dependent manner but, the molecular mechanism of this inhibition is not clear. Here, using computational methods including molecular docking and molecular dynamics simulation, also designing a cellular system that enabled us to trace Wnt-βcatenin kinetics directly, we investigated the mechanism of the peptide inhibitory potential against the pathway. Our computational results show that ANP can directly interact with FZD7 and also, its binding site on FZD7 overlap to the binding region of the Wnt carboxyl-terminal domain (Wnt-CTD). The finding of the silencing experiments demonstrates the dependency of Wnt-βcatenin signaling of the cellular system to FZD7. The decrease of βcatenin in cells treated to ANP and Wnt is also significant to compare to the control experiments. Finally, our results show that ANP is a potential scaffold to design selective peptide against FZD7.

Keywords: Frizzled7 receptor, Atrial natriuretic peptide, Wnt signaling

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