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The Role of Wnt and R-spondin in the Stomach During Health and Disease
Open AccessCommunication

The Function of Lgr5+ Cells in the Gastric Antrum Does Not Require Fzd7 or Myc In Vivo

1
University of Melbourne & Victorian Infectious Diseases Reference Laboratory, Doherty Institute of Infection and Immunity, Melbourne VIC 3000, Australia
2
Institute of Medical Biology, Singapore 138648, Singapore
3
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH8 9YL, UK
4
Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Heidelberg VIC 3084, Australia
5
School of Pharmacy and Biomedical Sciences, Curtin University, Perth WA 6845, Australia
6
European Cancer Stem Cell Research Institute, Cardiff University, Cardiff CF24 4HQ, UK
*
Authors to whom correspondence should be addressed.
Current address: Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
Biomedicines 2019, 7(3), 50; https://doi.org/10.3390/biomedicines7030050
Received: 7 June 2019 / Revised: 2 July 2019 / Accepted: 5 July 2019 / Published: 8 July 2019
(This article belongs to the Special Issue Gastric Cancer Research: From Basic Science to the Clinic)
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PDF [3320 KB, uploaded 8 July 2019]
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Abstract

The extreme chemical and mechanical forces endured by the gastrointestinal tract drive a constant renewal of the epithelial lining. Stem cells of the intestine and stomach, marked by the cell surface receptor Lgr5, preserve the cellular status-quo of their respective tissues through receipt and integration of multiple cues from the surrounding niche. Wnt signalling is a critical niche component for gastrointestinal stem cells and we have previously shown that the Wnt receptor, Frizzled-7 (Fzd7), is required for gastric homeostasis and the function of Lgr5+ intestinal stem cells. Additionally, we have previously shown a requirement for the Wnt target gene Myc in intestinal homeostasis, regeneration and tumourigenesis. However, it is unknown whether Fzd7 or Myc have conserved functions in gastric Lgr5+ stem cells. Here we show that gastric Lgr5+ stem cells do not require Fzd7 or Myc and are able to maintain epithelial homeostasis, highlighting key differences in the way Wnt regulates homeostasis and Lgr5+ stem cells in the stomach compared to the intestinal epithelium. Furthermore, deletion of Myc throughout the epithelium of the gastric antrum has no deleterious effects suggesting therapeutic targeting of Myc in gastric cancer patients will be well tolerated by the surrounding normal tissue. View Full-Text
Keywords: Wnt; gastric stem cells; Frizzled-7; Fzd7; Myc; Lgr5 Wnt; gastric stem cells; Frizzled-7; Fzd7; Myc; Lgr5
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Flanagan, D.; Barker, N.; Ernst, M.; Vincan, E.; Phesse, T. The Function of Lgr5+ Cells in the Gastric Antrum Does Not Require Fzd7 or Myc In Vivo. Biomedicines 2019, 7, 50.

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