| Literature DB >> 26585400 |
Yoku Hayakawa1, Hiroshi Ariyama1, Jitka Stancikova2, Kosuke Sakitani1, Samuel Asfaha1, Bernhard W Renz3, Zinaida A Dubeykovskaya1, Wataru Shibata1, Hongshan Wang1, Christoph B Westphalen1, Xiaowei Chen1, Yoshihiro Takemoto1, Woosook Kim1, Shradha S Khurana1, Yagnesh Tailor1, Karan Nagar1, Hiroyuki Tomita4, Akira Hara4, Antonia R Sepulveda5, Wanda Setlik6, Michael D Gershon6, Subhrajit Saha7, Lei Ding8, Zeli Shen9, James G Fox9, Richard A Friedman10, Stephen F Konieczny11, Daniel L Worthley1, Vladimir Korinek2, Timothy C Wang12.
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.Entities:
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Year: 2015 PMID： 26585400 PMCID： PMC4684751 DOI： 10.1016/j.ccell.2015.10.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743