Bluecher, Christina and Iberl, Sabine and Schwagarus, Nancy and Mueller, Silvana and Liebisch, Gerhard and Hoering, Marcus and Hidrobo, Maria Soledad and Ecker, Josef and Spindler, Nick and Dietrich, Arne and Burkhardt, Ralph and Stadler, Sonja C. (2020) Secreted Factors from Adipose Tissue Reprogram Tumor Lipid Metabolism and Induce Motility by Modulating PPAR alpha/ANGPTL4 and FAK. MOLECULAR CANCER RESEARCH, 18 (12). pp. 1849-1862. ISSN 1541-7786, 1557-3125
Full text not available from this repository. (Request a copy)Abstract
Recent studies indicate that adipose tissue in obesity promotes breast cancer progression by secreting protumorigenic chemokines, growth factors, and fatty acids. However, the detailed mechanisms by which hypertrophic adipose tissue influences breast cancer cells are still not well understood. Here we show that co-culture with adipose tissue from high-fat diet induced obese C57BL/6 mice alters transcriptome profiles in triple-negative breast cancer (TNBC) cells, leading to upregulation of genes involved in inflammation and lipid metabolism, such as IL1B, PLIN2, and ANGPTL4. Similar results were obtained by treating TNBC cells with adipose tissue conditioned media (ACM) generated from fat tissue of obese female patients. Many of the upregulated genes were activated by PPAR nuclear receptors, as shown by pathway analyses and gene expression experiments using PPAR agonists and antagonists. Metabolic analysis revealed that TNBC cells cultivated with ACM had significantly higher levels of beta-oxidation. Furthermore, ACM-treated TNBC cells displayed a pronounced aggressive cell phenotype, with enhanced wound healing, proliferation, and invasion capabilities. ACM-induced invasion was dependent on the PPAR-target ANGPTL4 and activated FAK signaling, as shown by ANGPTL4 depletion and FAK inhibition. Together, our data suggest that factors released by adipose tissue change PPAR-regulated gene expression and lipid metabolism and induce a more aggressive TNBC cell phenotype. These effects are, at least in parts, mediated by fatty acids provided by the adipose tissue.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BODY-MASS INDEX; BREAST-CANCER; ANOIKIS RESISTANCE; FATTY-ACIDS; OBESITY; METASTASIS; ANGPTL4; PROLIFERATION; BETA/DELTA; LIPOLYSIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 07:14 |
| Last Modified: | 08 Mar 2021 07:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43292 |
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