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- Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer
- Ji-Yoon Lee; M Nam; H Y Son; K Hyun; S Y Jang; Jong Woo Kim; Min Wook Kim; Y Jung; E Jang; S J Yoon; J Kim; J Kim; Jinho Seo; Jeong Ki Min; Kyoung-Jin Oh; Baek Soo Han; Won Kon Kim; Kwang-Hee Bae; J Song; J Kim; Y M Huh; G S Hwang; Eun-Woo Lee; Sang Chul Lee
- Bibliographic Citation
- Proceedings of National Academy of Sciences of United States of America, vol. 117, no. 51, pp. 32433-32442
- Publication Year
- Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
- Ferroptosis; Lipid peroxidation; ELOVL5; FADS1; Arachidonic acid
- Natl Acad Sciences
- Appears in Collections:
- Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
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