Faithin Omaha eBook Collection

Download or read book Evidence that Ligand Activation of Peroxisome Proliferator-activated Receptor-[beta]/[delta] (PPAR[beta]/[delta]) Inhibits TNF[alpha]-induced Epithelial-to-mesenchymal Transition by Modulation of SNAIL Expression and Stemness in Human Colon Cancer Cells written by Kevin Consevage and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Colorectal cancer patients with relatively higher expression of peroxisome proliferator-activated receptor [beta]/[delta] (PPAR[beta]/[delta]) in their primary tumors as compared to patients with relatively lower PPAR[beta]/[delta] expression exhibit lower propensity of metastasis and significantly increased survival. One of the mechanisms underlying cancer metastasis is the process of epithelial-to-mesenchymal transition (EMT). This study tested the hypothesis that ligand activation of PPAR[beta]/[delta] would inhibit EMT using a human colon carcinoma cell line (HCT116). EMT was induced in HCT116 cells by treating with tumor necrosis factor [alpha] (TNF[alpha]), and the influence of PPAR[beta]/[delta] was determined by examining the effect of the highly specific PPAR[beta]/[delta] agonist, GW0742, and/or antagonist, GSK3787. TNF[alpha] induced EMT in HCT116 cells at 36 hours as evidenced by the development of a mesenchymal-like morphology, a decrease in E-CADHERIN mRNA and protein expression and an increase in N-CADHERIN protein expression compared to controls. Ligand activation of PPAR[beta]/[delta] in HCT116 cells caused a decrease in TNF[alpha]-induced N-CADHERIN expression and an increase in E-CADHERIN protein expression compared to controls, but did not prevent morphological changes associated with EMT. Antagonizing PPAR[beta]/[delta] did not prevent the effects of ligand activation of PPAR[beta]/[delta] on EMT in HCT116 cells. Recently, EMT has been linked to the acquisition of cancer stem cell (CSC) phenotypes. Ligand activation of PPAR[beta]/[delta] caused a decrease in SNAIL mRNA expression as well as NANOG and OCT4 protein expression in HCT116 cells compared to controls. Collectively, results from this study provide evidence that ligand activation of PPAR[beta]/[delta] inhibits TNF[alpha]-induced EMT in HCT116 cells by modulating stemness.