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Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer
- Title
- Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer
- Authors
- Lee J.-Y.; Nam M.; Son H.Y.; Hyun K.; Jang S.Y.; Kim J.W.; Kim M.W.; Jung Y.; Jang E.; Yoon S.-J.; Kim J.; Seo J.; Min J.-K.; Oh K.-J.; Han B.-S.; Kim W.K.; Bae K.-H.; Song J.; Huh Y.-M.; Hwang G.-S.; Lee E.-W.; Lee S.C.
- Ewha Authors
- 황금숙
- SCOPUS Author ID
- 황금숙
- Issue Date
- 2020
- Journal Title
- Proceedings of the National Academy of Sciences of the United States of America
- ISSN
- 0027-8424
- Citation
- Proceedings of the National Academy of Sciences of the United States of America vol. 117, no. 51, pp. 32433 - 32442
- Keywords
- Arachidonic acid; ELOVL5; FADS1; Ferroptosis; Lipid peroxidation
- Publisher
- National Academy of Sciences
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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 longchain 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. © 2020 National Academy of Sciences. All rights reserved.
- DOI
- 10.1073/pnas.2006828117
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
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