PPAR? Mediates the Effect of Dietary Fat in Promoting Colorectal Cancer Metastasis.

ABSTRACT: The nuclear hormone receptor peroxisome proliferator-activated receptor delta (PPAR?) is a ligand-dependent transcription factor involved in fatty acid metabolism, obesity, wound healing, inflammation, and cancer. Although PPAR? has been shown to promote intestinal adenoma formation and growth, the molecular mechanisms underlying the contribution of PPAR? to colorectal cancer remain unclear. Here, we demonstrate that activation of PPAR? 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, PPAR? 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 PPAR?-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 PPAR? antagonists to therapeutically target CSCs in colorectal cancer. SIGNIFICANCE: These findings show that PPAR? contributes to colorectal cancer metastasis by expanding the CSC population, indicating that antagonists that target PPAR? may be beneficial in treating colorectal cancer.

SUBMITTER: Wang D 

PROVIDER: S-EPMC6726501 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature