Intrinsic temperature increase drives lipid metabolism towards ferroptosis evasion and chemotherapy resistance in pancreatic cancer.

Autor: de Laat V; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Topal H; Abdominal Surgical Oncology, University Hospitals Leuven, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Spotbeen X; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Talebi A; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Dehairs J; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Idkowiak J; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Vanderhoydonc F; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Ostyn T; Department of Pathology, University Hospitals Leuven, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Zhao P; Laboratory for Mechanisms of Cell Transformation, VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium., Jacquemyn M; Molecular Genetics and Therapeutics in Virology and Oncology, Rega Institute for Medical Research, KU Leuven Department of Microbiology and Immunology, Leuven, Belgium., Wölk M; Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany., Sablina A; Laboratory for Mechanisms of Cell Transformation, VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium., Augustyns K; Department of Pharmaceutical Sciences, Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium., Vanden Berghe T; Department of Biomedical Molecular Biology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Roskams T; Department of Pathology, University Hospitals Leuven, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Daelemans D; Molecular Genetics and Therapeutics in Virology and Oncology, Rega Institute for Medical Research, KU Leuven Department of Microbiology and Immunology, Leuven, Belgium., Fedorova M; Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany., Topal B; Abdominal Surgical Oncology, University Hospitals Leuven, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Swinnen JV; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium. j.swinnen@kuleuven.be.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 02; Vol. 15 (1), pp. 8540. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1038/s41467-024-52978-z
Abstrakt: A spontaneously occurring temperature increase in solid tumors has been reported sporadically, but is largely overlooked in terms of cancer biology. Here we show that temperature is increased in tumors of patients with pancreatic ductal adenocarcinoma (PDAC) and explore how this could affect therapy response. By mimicking this observation in PDAC cell lines, we demonstrate that through adaptive changes in lipid metabolism, the temperature increase found in human PDAC confers protection to lipid peroxidation and contributes to gemcitabine resistance. Consistent with the recently uncovered role of p38 MAPK in ferroptotic cell death, we find that the reduction in lipid peroxidation potential following adaptation to tumoral temperature allows for p38 MAPK inhibition, conferring chemoresistance. As an increase in tumoral temperature is observed in several other tumor types, our findings warrant taking tumoral temperature into account in subsequent studies related to ferroptosis and therapy resistance. More broadly, our findings indicate that tumoral temperature affects cancer biology.
(© 2024. The Author(s).)
Databáze: MEDLINE
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