Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche
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Fox_Mist1 expressing.pdf
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Checksum (MD5)
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Author(s)
Hayakawa, Yoku
Ariyama, Hiroshi
Stancikova, Jitka
Sakitani, Kosuke
Asfaha, Samuel
Renz, Bernhard W.
Dubeykovskaya, Zinaida A.
Shibata, Wataru
Wang, Hongshan
Westphalen, Christoph B.
Date Issued
November 2015
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.ccell.2015.10.003
