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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Hayakawa Y,Ariyama H,Stancikova J,Sakitani K,Asfaha S,Renz BW,Dubeykovskaya ZA,Shibata W,Wang H,Westphalen CB,Chen X,Takemoto Y,Kim W,Khurana SS,Tailor Y,Nagar K,Tomita H,Hara A,Sepulveda AR,Setlik W,Gershon MD,doi
10.1016/j.ccell.2015.10.003subject
Has Abstractpub_date
2015-12-14 00:00:00pages
800-814issue
6eissn
1535-6108issn
1878-3686pii
S1535-6108(15)00380-3journal_volume
28pub_type
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