RT Journal Article
SR Electronic
T1 PPARD regulation in gastric progenitor cells drives gastric tumorigenesis in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 218214
DO 10.1101/218214
A1 Xiangsheng Zuo
A1 Yasunori Deguchi
A1 Weiguo Xu
A1 Daoyan Wei
A1 Rui Tian
A1 Weidong Chen
A1 Micheline J. Moussalli
A1 Yi Liu
A1 Fei Mao
A1 Min Xu
A1 Yaying Yang
A1 Shen Gao
A1 Jonathan C. Jaoude
A1 Fuyao Liu
A1 Mihai Gagea
A1 Russell Broaddus
A1 Keping Xie
A1 Imad Shureiqi
YR 2017
UL http://biorxiv.org/content/early/2017/11/12/218214.abstract
AB Little is known about the cell origin of gastric cancer. Peroxisome proliferator-activated receptor-delta (PPARD) is a druggable ligand-activated nuclear receptor that impacts protumorigenic cellular events. However, PPARD’s role in tumorigenesis, especially gastric tumorigenesis, remains to be defined. We found that targeting PPARD overexpression in murine gastric progenitor cells (GPC), via a villin promoter, spontaneously induced gastric tumorigenesis that progressed to invasive adenocarcinoma. PPARD overexpression in GPC upregulated tumorigenic proinflammatory cytokine and CD44 expression, expanded GPC population in vivo, enhanced GPC self-renewal and proliferation in organoid cultures, and endowed these cells with tumorigenic properties. Our findings identify PPARD as a driver of gastric tumorigenesis via GPC transformation.