Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche

Author(s)
Hayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka; Sakitani, Kosuke; Asfaha, Samuel; ... Show more
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Abstract
The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1⁺ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12⁺ endothelial cells and Cxcr4⁺ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.
Date issued
2015-11
URI
http://hdl.handle.net/1721.1/107766
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Division of Comparative Medicine
Journal
Cancer Cell
Publisher
Elsevier
Citation
Hayakawa, Yoku et al. “Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.” Cancer Cell 28.6 (2015): 800–814.
Version: Author's final manuscript
ISSN
1535-6108
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