ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Induction of Fatty Acid Oxidation Underlies DNA Damage-Induced Cell Death and Ameliorates Obesity-Driven Chemoresistance.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 9 citations in OpenAlex.
- Cannabigerol and Cannabichromene Induce Lung Cancer Cell Death and Apoptosis-Contribution of PPARα to Cannabigerol Effects.Antioxidants (Basel, Switzerland) · 2026Article
- Understanding the Interplay Between Obesity and Cancer: From Mechanisms to Therapeutic Opportunities.Cancers · 2026Review
- ATGL sensitizes hepatocellular carcinoma cells to genotoxic drugs by modulating p53 acetylation/phosphorylation status.Cell death discovery · 2026Article
- Article
- Multi-omics analysis identifies PPARα as a key inhibitor of hepatocyte ferroptosis in sepsis-associated liver injury.PloS one · 2026Article
- Beyond Bioenergetics: Emerging Roles of Mitochondrial Fatty Acid Oxidation in Stress Response and Aging.Cells · 2025Review
- Translational Aspects of DNA Damage Repair in Optimizing Cancer Chemotherapy.Advanced genetics (Hoboken, N.J.) · 2025Review
- The role and mechanism of fatty acid oxidation in cancer drug resistance.Cell death discovery · 2025Review
- Clinical approaches to overcome PARP inhibitor resistance.Molecular cancer · 2025Review
- Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer.World journal of gastroenterology · 2025Article
- Induction of Fatty Acid Oxidation Underlies DNA Damage-Induced Cell Death and Ameliorates Obesity-Driven Chemoresistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
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.
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Registered trials
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