PPARδ and PGE2signaling pathways communicate and connect inflammation to colorectal cancer.
The nuclear hormone receptor peroxisome proliferator-activated receptor δ (PPARδ) is a ligand-dependent transcription factor that is involved in fatty acid metabolism, obesity, wound healing, inflammation, and cancer. Despite decades of research, the role of PPARδ in inflammation and colorectal cancer remains unclear and somewhat controversial. Our recent work presented the first genetic evidence demonstrating that PPARδ is required for chronic colonic inflammation and colitis-associated carcinogenesis. We also found that a PPARδ downstream pathway, namely the COX-2-derived PGE2signaling, mediated crosstalk between tumor epithelial cells and macrophages to promote chronic inflammation and colitis-associated tumor genesis. In this brief review, we summarize recent studies on the role of PPARδ in inflammatory bowel disease (IBD) and colorectal cancer (CRC) and highlight recent advances in our understanding of how PPARδ and COX-2-drevided PGE2signaling coordinately promote chronic colonic inflammation and colitis-associate tumorigenesis. Elucidating the role of PPARδ in inflammation and CRC may provide a rationale for development of PPARδ antagonists as new therapeutic agents in treatment of IBD and CRC.
Laboratory for Inflammation and Cancer, the Biodesign Institute at Arizona State University, Tempe, AZ 85287.
Dingzhi
D
Wang
Laboratory for Inflammation and Cancer, the Biodesign Institute at Arizona State University, Tempe, AZ 85287 ; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 ; Department of Research and Division of Gastroenterology, Mayo Clinic, Scottsdale, AZ 85259.
Raymond N
RN
DuBois
Colorectal cancer; and COX-2-drived PGE2; chemokines; colitis-associated tumorigenesis; inflammation; peroxisome proliferator-activated receptor