| First Author | Wang D | Year | 2019 |
| Journal | Cancer Res | Volume | 79 |
| Issue | 17 | Pages | 4480-4490 |
| PubMed ID | 31239272 | Mgi Jnum | J:278957 |
| Mgi Id | MGI:6359608 | Doi | 10.1158/0008-5472.CAN-19-0384 |
| Citation | Wang D, et al. (2019) PPARdelta Mediates the Effect of Dietary Fat in Promoting Colorectal Cancer Metastasis. Cancer Res 79(17):4480-4490 |
| abstractText | The nuclear hormone receptor peroxisome proliferator-activated receptor delta (PPARdelta) is a ligand-dependent transcription factor involved in fatty acid metabolism, obesity, wound healing, inflammation, and cancer. Although PPARdelta has been shown to promote intestinal adenoma formation and growth, the molecular mechanisms underlying the contribution of PPARdelta to colorectal cancer remain unclear. Here, we demonstrate that activation of PPARdelta induces expansion of colonic cancer stem cells (CSC) and promotes colorectal cancer liver metastasis by binding to the Nanog promoter and enhancing Nanog expression. Moreover, PPARdelta mediated the effect of a high-fat diet in promoting liver metastasis and induction of colonic CSC expansion. Our findings uncover a novel role of dietary fats in colorectal cancer metastasis and reveal novel mechanisms underlying PPARdelta-mediated induction of CSCs and those responsible for the contribution of dietary fats to colorectal cancer progression. These findings may provide a rationale for developing PPARdelta antagonists to therapeutically target CSCs in colorectal cancer. SIGNIFICANCE: These findings show that PPARdelta contributes to colorectal cancer metastasis by expanding the CSC population, indicating that antagonists that target PPARdelta may be beneficial in treating colorectal cancer. |
