Metastasis regulation by PPARD expression in cancer cells

• DOI: 10.1172/jci.insight.91419
• Publication Date: 2017-01-11T16:00:40Z
• Authors: Xiangsheng Zuo; Weiguo Xu; Min Xu; Rui Tian; Micheline J. Mous...; Fei Mao; Xiaofeng Zheng; Jing Wang; Jeffrey S. Morris; Mihai Gagea; Cathy Eng; Scott Kopetz; Dipen M. Maru; Asif Rashid; Russell Broaddus; Daoyan Wei; Mien-Chie Hung; Anil K. Sood; Imad Shureiqi
• Keywords: Periostin

Peroxisome proliferator–activated receptor–δ (PPARD) is upregulated in many major human cancers, but the role that its expression cancer cells has metastasis remains poorly understood. Here, we show specific PPARD downregulation or genetic deletion of significantly repressed various models vivo. Mechanistically, promoted angiogenesis via interleukin 8 vivo and vitro. Analysis transcriptome profiling HCT116 colon with without gene patterns The Cancer Genome Atlas colorectal adenocarcinoma database identified novel pro-metastatic genes (GJA1, VIM, SPARC, STC1, SNCG) as targets. drastically affected epithelial-mesenchymal transition, migration, invasion, further underscoring necessity for metastasis. Clinically, high cancers (e.g., colorectal, lung, breast) was associated reduced metastasis-free survival. Our results demonstrate PPARD, a druggable protein, an important molecular target metastatic cancer.