Figure 6 from PPARδ Orchestrates a Prometastatic Metabolic Response to Microenvironmental Cues in Pancreatic Cancer

作者：Beatriz Parejo-Alonso, David Barneda, Sara Maria David Trabulo, Sarah Courtois, Sara Compte-Sancerni, Jelena Zurkovic, Laura Ruíz-Cañas, Quan Zheng, Jiajia Tang, Matthias M. Gaida, Ulf Schmitz, Pilar Irún, Laure Penin-Peyta, Shanthini Mary Crusz, Petra Jagušt, Pilar Espiau-Romera, Alba Royo-García, Andrés Gordo-Ortiz, Mariia Yuneva, Meng‐Lay Lin, Shenghui Huang, Ming-Hsin Yang, Ángel Lanas, Bruno Sáinz, Christoph Thiele, Christopher Heeschen, Patricia Sancho · 年份：2025 · DOI：10.1158/0008-5472.30029483 · 研究领域：Peroxisome Proliferator-Activated Receptors、Cancer, Lipids, and Metabolism、Cancer, Hypoxia, and Metabolism

<p>PPARδ rewires cellular metabolism regulating <i>MYC/PGC1A</i> balance. <b>A,</b> Expression of <i>MYC</i>, <i>PGC1A</i>, and <i>MYC/PGC1A</i> ratio in PDX-354 after mitochondrial energy deprivation during 48 to 72 hours (<i>n</i> = 4–7). <b>B,</b><i>MYC</i> and <i>PGC1A</i> reporter assay. Promoter activity was estimated as luciferase bioluminescence at the indicated times following treatment with PPARδ agonist GW0742 or <i>PPARD</i> overexpression (<i>PPARD</i> OE; <i>n</i> = 3–5). <b>C,</b> PDAC-354 cells were transduced with inducible lentiviral vectors expressing either a nontargeting short hairpin RNA (NT shRNA) or two different shRNAs against <i>MYC</i> (sh#1 and sh#2) or the complete cDNA of <i>PGC1A</i>. Effect of<i> MYC</i> knockdown (shMYC, pooled data for sh#1 and sh#2) or <i>PGC1A</i> overexpression (<i>PGC1A</i> OE) on invasiveness in response to treatment with 5 μmol/L PPARδ agonist L-165 for 48 hours (<i>n</i> = 6–8). <b>D,</b> CUT&Tag analysis of MYC protein binding at the <i>CCNE</i>, <i>PGC1A</i>, <i>SNAI2</i>, and <i>VIM</i> loci. WashU Epigenome Browser tracks showing CUT&TAG signals at the mentioned loci with the indicated transcription start site (TSS). B...