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

Autor: Vincent de Laat, Halit Topal, Xander Spotbeen, Ali Talebi, Jonas Dehairs, Jakub Idkowiak, Frank Vanderhoydonc, Tessa Ostyn, Peihua Zhao, Maarten Jacquemyn, Michele Wölk, Anna Sablina, Koen Augustyns, Tom Vanden Berghe, Tania Roskams, Dirk Daelemans, Maria Fedorova, Baki Topal, Johannes V. Swinnen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-52978-z
Popis: Abstract 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.
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