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Cancers 2016, 8(5), 50;

Frizzled7: A Promising Achilles’ Heel for Targeting the Wnt Receptor Complex to Treat Cancer

1,2,†,‡,* , 1,†
Molecular Oncology Laboratory, Victorian Infectious Diseases Reference Laboratory and the Doherty Institute, University of Melbourne, Melbourne, VIC 3000, Australia
Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
School of Biomedical Sciences, Curtin University, Perth, WA 6102, Australia
These authors contributed equally to this work.
Current Address: European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, CF24 4HQ, UK
Authors to whom correspondence should be addressed.
Academic Editors: Renée van Amerongen and Walter Birchmeier
Received: 31 March 2016 / Revised: 3 May 2016 / Accepted: 9 May 2016 / Published: 17 May 2016
(This article belongs to the Special Issue Wnt Signaling in Cancer)
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Frizzled7 is arguably the most studied member of the Frizzled family, which are the cognate Wnt receptors. Frizzled7 is highly conserved through evolution, from Hydra through to humans, and is expressed in diverse organisms, tissues and human disease contexts. Frizzled receptors can homo- or hetero-polymerise and associate with several co-receptors to transmit Wnt signalling. Notably, Frizzled7 can transmit signalling via multiple Wnt transduction pathways and bind to several different Wnt ligands, Frizzled receptors and co-receptors. These promiscuous binding and functional properties are thought to underlie the pivotal role Frizzled7 plays in embryonic developmental and stem cell function. Recent studies have identified that Frizzled7 is upregulated in diverse human cancers, and promotes proliferation, progression and invasion, and orchestrates cellular transitions that underscore cancer metastasis. Importantly, Frizzled7 is able to regulate Wnt signalling activity even in cancer cells which have mutations to down-stream signal transducers. In this review we discuss the various aspects of Frizzled7 signalling and function, and the implications these have for therapeutic targeting of Frizzled7 in cancer. View Full-Text
Keywords: Wnt; cancer; Frizzled; Frizzled7; FZD7; Fz7; therapy; cell signalling; receptor; PCP Wnt; cancer; Frizzled; Frizzled7; FZD7; Fz7; therapy; cell signalling; receptor; PCP

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Phesse, T.; Flanagan, D.; Vincan, E. Frizzled7: A Promising Achilles’ Heel for Targeting the Wnt Receptor Complex to Treat Cancer. Cancers 2016, 8, 50.

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