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

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

Authors :
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
Source :
Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.8f15dc65565c4b5099ae63fd1bafc0fa
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-024-52978-z