bioRxivCancer BiologyPreprint
PPARD regulation in gastric progenitor cells drives gastric tumorigenesis in mice
Xiangsheng Zuo, Yasunori Deguchi, Weiguo Xu, Daoyan Wei, Rui Tian, Weidong Chen, Micheline J. Moussalli, Yi LiuiD, Fei Mao, Min XuiD, Yaying Yang, Shen Gao, Jonathan C. Jaoude, Fuyao Liu, Mihai Gagea, Russell Broaddus, Keping Xie, Imad Shureiqi
Abstract
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, PPARDs 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.
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