Abstract 844: PPARD downregulation in cancer cells suppresses metastases by inhibiting tumor angiogenesis and EMT

Abstract PPARD is upregulated in many major human cancers, but the role that its expression in cancer cells has in metastasis remains poorly understood. Here, we show that specific PPARD downregulation or genetic deletion of PPARD in cancer cells significantly repressed metastasis in various cancer models in vivo. Mechanistically, PPARD promoted angiogenesis via interleukin 8 in vivo and in vitro. Analysis of transcriptome profiling of HCT116 colon cancer cells with or without genetic deletion of PPARD and gene expression patterns in The Cancer Genome Atlas colorectal adenocarcinoma database identified novel pro-metastatic genes (GJA1, VIM, SPARC, STC1, SNCG) as PPARD targets. PPARD expression in cancer cells drastically affected epithelial-mesenchymal transition, migration, and invasion, further underscoring its necessity to metastasis. Clinically, high PPARD expression in various major human cancers (e.g., colorectal, lung, breast) was associated with significantly reduced metastasis-free survival. Our results demonstrate that PPARD, a druggable protein, is an important molecular target in metastatic cancer. Citation Format: Xiangsheng Zuo, Weiguo Xu, Min Xu, Rui Tian, Micheline J. Moussalli J. Moussalli, Fei Mao, Mihai Gagea, Daoyan Wei, Anil K. Sood, Imad Shureiqi. PPARD downregulation in cancer cells suppresses metastases by inhibiting tumor angiogenesis and EMT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 844. doi:10.1158/1538-7445.AM2017-844