Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cancer cell, 2015-12, Vol.28 (6), p.800-814

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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. [Display omitted] •Quiescent Mist1+ stem cells reside in the corpus isthmus•Mist1+ stem cells are a cellular origin of gastric cancers•Cxcl12/Cxcr4 perivascular niche supports isthmus stem cells•Wnt5a from Cxcr4+ ILCs promotes diffuse cancer development Hayakawa et al. show that Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs) form a perivascular niche to support diffuse-type gastric cancer (DGC) development from Mist1-expressing gastric stem cells through Wnt5a produced by ILCs. Targeting ILCs, Cxcr4, or Wnt5a inhibits DGC development.