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

Yoku Hayakawa, Hiroshi Ariyama, Jitka Stancikova, Kosuke Sakitani, Samuel Asfaha, Bernhard W. Renz, Zinaida A. Dubeykovskaya, Wataru Shibata, Hongshan Wang, Christoph B. Westphalen, Xiaowei Chen, Yoshihiro Takemoto, Woosook Kim, Shradha S. Khurana, Yagnesh Tailor, Karan Nagar, Hiroyuki Tomita, Akira Hara, Antonia R. Sepulveda, Wanda SetlikMichael D. Gershon, Subhrajit Saha, Lei Ding, Zeli Shen, James G. Fox, Richard A. Friedman, Stephen F. Konieczny, Daniel L. Worthley, Vladimir Korinek, Timothy C. Wang

Research output: Contribution to journalArticle

125 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)800-814
Number of pages15
JournalCancer Cell
Volume28
Issue number6
DOIs
Publication statusPublished - 14 Dec 2015

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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