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Title: The Function of Lgr5+ Cells in the Gastric Antrum Does Not Require Fzd7 or Myc In Vivo.
Austin Authors: Flanagan, Dustin;Barker, Nick;Ernst, Matthias ;Vincan, Elizabeth;Phesse, Toby
Affiliation: University of Melbourne & Victorian Infectious Diseases Reference Laboratory, Doherty Institute of Infection and Immunity, Melbourne VIC 3000, Australia
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH8 9YL, UK
School of Pharmacy and Biomedical Sciences, Curtin University, Perth WA 6845, Australia
Institute of Medical Biology, Singapore 138648, Singapore
Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
European Cancer Stem Cell Research Institute, Cardiff University, Cardiff CF24 4HQ, UK
Issue Date: 8-Jul-2019 2019-07-08
Publication information: Biomedicines 2019; 7(3): E50
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.
DOI: 10.3390/biomedicines7030050
ORCID: 0000-0002-8607-4849
PubMed URL: 31288403
ISSN: 2227-9059
Type: Journal Article
Subjects: Frizzled-7
gastric stem cells
Appears in Collections:Journal articles

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