Journal article

Frizzled-7 Is Required for Wnt Signaling in Gastric Tumors with and Without Apc Mutations

Dustin J Flanagan, Nick Barker, Natasha S Di Costanzo, Elizabeth A Mason, Austin Gurney, Valerie S Meniel, Sarah Koushyar, Chloe R Austin, Matthias Ernst, Helen B Pearson, Alex Boussioutas, Hans Clevers, Toby J Phesse, Elizabeth Vincan

CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2019

Abstract

A subset of patients with gastric cancer have mutations in genes that participate in or regulate Wnt signaling at the level of ligand (Wnt) receptor (Fzd) binding. Moreover, increased Fzd expression is associated with poor clinical outcome. Despite these findings, there are no in vivo studies investigating the potential of targeting Wnt receptors for treating gastric cancer, and the specific Wnt receptor transmitting oncogenic Wnt signaling in gastric cancer is unknown. Here, we use inhibitors of Wnt/Fzd (OMP-18R5/vantictumab) and conditional gene deletion to test the therapeutic potential of targeting Wnt signaling in preclinical models of intestinal-type gastric cancer and ex vivo organoid..

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by Melbourne Health project grants


Awarded by Medical Research Council


Awarded by Early career researcher grant


Awarded by Cancer Council of Victoria (CCV)


Funding Acknowledgements

We thank Damian Neate and Jean Moselen for technical assistance. We also thank John Mariadason, Cameron Nowell, Christine Wells, Trevelyan Menheniott, Matthias Ernst, Stefen Glaser, and Andy Giraud for gifting cell lines, plasmids, mutant mice, microscopy assistance, and critical discussion. Funding is gratefully acknowledged from the following: National Health and Medical Research Council of Australia (NHMRC, 566679, and APP1099302 awarded to E. Vincan, T.J. Phesse, and N. Barker), Melbourne Health project grants (605030 and PG-002 awarded to E. Vincan, T.J. Phesse, N. Barker and H. Clevers), Medical Research Council (MR/R026424/1 to T.J. Phesse), and Early career researcher grant (GIA-033 awarded to D.J. Flanagan), Cancer Council of Victoria project grants (CCV, APP1020716 awarded to E. Vincan, T.J. Phesse, and N. Barker), CCV Fellowship awarded to D.J. Flanagan and Cardiff University/CMU Research Fellowship awarded to T.J. Phesse.