Frizzled7 Activates β-Catenin-Dependent and β-Catenin-Independent Wnt Signalling Pathways During Developmental Morphogenesis: Implications for Therapeutic Targeting in Colorectal Cancer

Bang Manh Tran; Dustin James Flanagan; Toby James Phesse; Elizabeth Vincan

doi:10.1007/164_2021_524

Frizzled₇ Activates β-Catenin-Dependent and β-Catenin-Independent Wnt Signalling Pathways During Developmental Morphogenesis: Implications for Therapeutic Targeting in Colorectal Cancer

Handb Exp Pharmacol. 2021:269:251-277. doi: 10.1007/164_2021_524.

Authors

Bang Manh Tran^{1

2}, Dustin James Flanagan^{2

3}, Toby James Phesse^{2

4}, Elizabeth Vincan^{5

6

7

8}

Affiliations

¹ Department of Infectious Diseases, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
² The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
³ Cancer Research UK Beatson Institute, Glasgow, UK.
⁴ European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, UK.
⁵ Department of Infectious Diseases, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia. evincan@unimelb.edu.au.
⁶ The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. evincan@unimelb.edu.au.
⁷ Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. evincan@unimelb.edu.au.
⁸ Curtin Medical School, Curtin University, Perth, WA, Australia. evincan@unimelb.edu.au.

PMID: 34455486
DOI: 10.1007/164_2021_524

Abstract

Frizzled₇ activates β-catenin-dependent and β-catenin-independent Wnt signalling pathways, is highly conserved through evolution from the ancient phylum hydra to man, plays essential roles in stem cells, tissue homeostasis and regeneration in the adult, and is upregulated in diverse cancers. Much of what is known about the core components of the Wnt signalling pathways was derived from studying the function of Frizzled₇ orthologues in the development of lower organism. As we interrogate Frizzled₇ signalling and function for therapeutic targeting in cancer, it is timely to revisit lower organisms to gain insight into the context dependent and dynamic nature of Wnt signalling for effective drug design.

Keywords: Cancer; Drug discovery; FZD; FZD7; Frizzled; Frizzled7; PCP; Wnt; Wnt/Ca++ pathway; β-catenin.

MeSH terms

Animals
Colorectal Neoplasms* / drug therapy
Frizzled Receptors*
Humans
Morphogenesis*
Wnt Signaling Pathway*
beta Catenin* / metabolism

Substances

Frizzled Receptors
beta Catenin