Citations

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

Lung cancer is one of the most common types of human malignancies and the leading cause of cancer-related death. Patients with surgically resectable early stage lung cancer are more likely curable, but currently only a small population of patients can be diagnosed at such a stage, partly due to our incomplete understanding of the biology of lung cancer and the lack of diagnostic and prognostic biomarkers. Recent studies have shown that NOTCH1 is a critical regulator of human carcinogenesis and has been implicated in multiple steps of cancer development and progression. Herein, we review recent findings about the role of NOTCH1 in lung cancer and discuss its potential usefulness as both a therapeutic target and a biomarker for lung cancer.