Induction of Fatty Acid Oxidation Underlies DNA Damage‐Induced Cell Death and Ameliorates Obesity‐Driven Chemoresistance
Abstract: The DNA damage response is essential for preserving genome integrity and eliminating damaged cells. Although cellular metabolism plays a central role in cell fate decision between proliferation, survival, or death, the metabolic response to DNA damage remains largely obscure. Here, this work shows that DNA damage induces fatty acid oxidation (FAO), which is required for DNA damage‐induced cell death. Mechanistically, FAO induction increases cellular acetyl‐CoA levels and promotes N‐alpha‐acetylation of caspase‐2, leading to cell death. Whereas chemotherapy increases FAO related genes through peroxisome proliferator‐activated receptor α (PPARα), accelerated hypoxia‐inducible factor‐1α stabilization by tumor cells in obese mice impedes the upregulation of FAO, which contributes to its chemoresistance. Finally, this work finds that improving FAO by PPARα activation ameliorates obesity‐driven chemoresistance and enhances the outcomes of chemotherapy in obese mice. These findings reveal the shift toward FAO induction is an important metabolic response to DNA damage and may provide effective therapeutic strategies for cancer patients with obesity.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Induction of Fatty Acid Oxidation Underlies DNA Damage‐Induced Cell Death and Ameliorates Obesity‐Driven Chemoresistance ; day:25 ; month:12 ; year:2023 ; extent:14
Advanced science ; (25.12.2023) (gesamt 14)
- Urheber
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Hwang, Sunsook
Yang, Seungyeon
Park, Kyungsoo
Kim, Byungjoo
Kim, Minjoong
Shin, Seungmin
Yoo, Ahyoung
Ahn, Jiyun
Jang, Juneil
Yim, Yeong Shin
Seong, Rho H.
Jeong, Seung Min
- DOI
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10.1002/advs.202304702
- URN
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urn:nbn:de:101:1-2023122614041909476470
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:37 MESZ
Datenpartner
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Beteiligte
- Hwang, Sunsook
- Yang, Seungyeon
- Park, Kyungsoo
- Kim, Byungjoo
- Kim, Minjoong
- Shin, Seungmin
- Yoo, Ahyoung
- Ahn, Jiyun
- Jang, Juneil
- Yim, Yeong Shin
- Seong, Rho H.
- Jeong, Seung Min
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