Figure 2 from PPARδ Orchestrates a Prometastatic Metabolic Response to Microenvironmental Cues in Pancreatic Cancer
<p>Transcriptomic and scRNA-seq analyses identify metabolic switch and EMT induction upon pseudostarvation. Cells were treated for 48 hours with vehicle (Ctrl), MCM, and 20 μmol/L etomoxir (Eto). <b>A,</b> Gene expression profile as assessed by a carbohydrate metabolism PCR array in PDAC-354 cells. Heatmap showing only genes whose expression was significantly altered (<i>n</i> = 3). <b>B,</b> Left, PDAC-003 cells were treated as indicated and were then subjected to scRNA-seq (10X Genomics Chromium platform). Unsupervised clustering of viable PDAC cells exposed to Ctrl, MCM, or etomoxir, represented as Uniform Manifold Approximation and Projection (UMAP) plots. Different clusters are color-coded. Right, boxplots illustrating gene set enrichment results for the EMT and glycolysis (Hallmark data set) for different clusters in Ctrl vs. MCM and etomoxir treatment, respectively. Differences in enrichment scores between treatments were assessed using the Mann–Whitney <i>U</i> test. <b>C,</b> Expression of EMT hallmark signature and <i>PPARD</i> in single cancer cells (PDAC-002 and 021) displayed as unsupervised clusters and color-coded for allocated treatment. See also Supplementary Figs. S4 and S5.</p>
Authors
- Mariia Yuneva (ORCID: https://orcid.org/0000-0003-3455-9374)
- Petra Jagušt (ORCID: https://orcid.org/0000-0001-5291-251X)
- Jelena Zurkovic (ORCID: https://orcid.org/0000-0002-5932-4849)
- David Barneda (ORCID: https://orcid.org/0000-0002-4436-4100)
- Bruno Sáinz (ORCID: https://orcid.org/0000-0003-4829-7651)
- Patricia Sancho (ORCID: https://orcid.org/0000-0002-1092-5395)
- Beatriz Parejo-Alonso (ORCID: https://orcid.org/0000-0002-5393-4283)
- Laura Ruíz-Cañas (ORCID: https://orcid.org/0000-0002-4373-2573)
- Matthias M. Gaida (ORCID: https://orcid.org/0000-0003-1499-7772)
- Sara Maria David Trabulo (ORCID: https://orcid.org/0000-0002-3178-2119)
- Shanthini Mary Crusz (ORCID: https://orcid.org/0000-0003-0687-0149)
- Pilar Espiau-Romera (ORCID: https://orcid.org/0000-0002-7165-199X)
- Christopher Heeschen (ORCID: https://orcid.org/0000-0002-1158-8554)
- Sara Compte-Sancerni (ORCID: https://orcid.org/0000-0003-2297-7368)
- Sarah Courtois (ORCID: https://orcid.org/0000-0001-8572-2499)
- Pilar Irún (ORCID: https://orcid.org/0000-0003-3392-7200)
- Ulf Schmitz (ORCID: https://orcid.org/0000-0001-5806-4662)
- Laure Penin-Peyta
- Ming-Hsin Yang (ORCID: https://orcid.org/0000-0001-9093-1009)
- Ángel Lanas (ORCID: https://orcid.org/0000-0001-5932-2889)
- Meng‐Lay Lin (ORCID: https://orcid.org/0000-0002-1187-1050)
- Alba Royo-García (ORCID: https://orcid.org/0000-0002-5079-6890)
- Jiajia Tang (ORCID: https://orcid.org/0000-0002-7775-827X)
- Quan Zheng (ORCID: https://orcid.org/0000-0002-4512-9233)
- Christoph Thiele (ORCID: https://orcid.org/0000-0001-5161-2558)
- Shenghui Huang (ORCID: https://orcid.org/0000-0002-3714-1961)
- Andrés Gordo-Ortiz
Publication Details
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1158/0008-5472.30029498
- Primary Topic
- Peroxisome Proliferator-Activated Receptors
- Type
- article
- Field-Weighted Citation Impact
- 0.00