title: Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the PPAR-δ Pathway.
abstract: Peroxisome proliferator-activated receptor delta (PPAR-δ) is a nuclear receptor transcription factor that regulates gene expression during development and disease states, such as cancer. However, the precise role of PPAR-δ during tumorigenesis is not well understood. Recent data suggest that PPAR-δ may have context-specific oncogenic and tumor-suppressive roles depending on the tissue, cell-type, or diet-induced physiology in question. For example, in the intestine, pro-obesity diets, such as a high-fat diet (HFD), are associated with increased colorectal cancer incidence. Interestingly, many of the effects of an HFD in the stem and progenitor cell compartment are driven by a robust PPAR-δ program and contribute to the early steps of intestinal tumorigenesis. Importantly, the PPAR-δ pathway or its downstream mediators may serve as therapeutic intervention points or biomarkers in colon cancer that arise in patients who are obese. Although potent PPAR-δ agonists and antagonists exist, their clinical utility may be enhanced by uncovering how PPAR-δ mediates tumorigenesis in diverse tissues and cell types as well as in response to diet. Clin Cancer Res; 22(23); 5636-41. ©2016 AACR.
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.|Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Semir
authors.initials: S
authors.lastname: Beyaz
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts. ohyilmaz@mit.edu.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.|Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ömer H
authors.initials: ÖH
authors.lastname: Yilmaz
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology*; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D047494:PPAR delta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D047494:PPAR delta