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PPARD regulation in gastric progenitor cells drives gastric tumorigenesis in mice

Year: 2017
Type: preprint
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, 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.
DOI: 10.1101/218214
Authors: Xiangsheng Zuo, Yasunori Deguchi, Weiguo Xu, Daoyan Wei, Rui Tian, Weidong Chen, Micheline J. Moussalli, Yi Liu, Fei Mao, Min Xu, Yaying Yang, Shen Gao, Jonathan C. Jaoude, Fuyao Liu, Mihai Gagea, Russell Broaddus, Keping Xie, Imad Shureiqi
Language: English
Open Access status: green
Awards: G1093731028, G1468253849, G1867270842, G1901027039, G2834394994, G3400514463, G788993117, PPAR-Delta Regulation of Wnt/B-Catenin To Drive Colon Cancer
OpenAlex ID: W2767302522
Cites: 16
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Related to: 10