Hormonal Suppression of Stem Cells Inhibits Symmetric Cell Division and Gastric Tumorigenesis.

Cell Stem Cell
Wenju ChangTimothy C Wang

Abstract

Cancer is believed to arise from stem cells, but mechanisms that limit the acquisition of mutations and tumor development have not been well defined. We show that a +4 stem cell (SC) in the gastric antrum, marked by expression of Cck2r (a GPCR) and Delta-like ligand 1 (DLL1), is a label-retaining cell that undergoes predominant asymmetric cell division. This +4 antral SC is Notch1low/ Numb+ and repressed by signaling from gastrin-expressing endocrine (G) cells. Chemical carcinogenesis of the stomach is associated with loss of G cells, increased symmetric stem cell division, glandular fission, and more rapid stem cell lineage tracing, a process that can be suppressed by exogenous gastrin treatment. This hormonal suppression is associated with a marked reduction in gastric cancer mutational load, as revealed by exomic sequencing. Taken together, our results show that gastric tumorigenesis is associated with increased symmetric cell division that facilitates mutation and is suppressed by GPCR signaling.

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Citations

Jun 11, 2020·Cancer Science·Yukiko OyaKazuhiko Koike
Jun 1, 2021·Gastrointestinal Endoscopy Clinics of North America·Judith Kim, Timothy Cragin Wang
Jun 16, 2021·Cell Stem Cell·Yoku HayakawaTimothy C Wang

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