| Literature DB >> 33288688 |
Ji-Yoon Lee1,2, Miso Nam3, Hye Young Son4, Kwangbeom Hyun1, Seo Young Jang3,5, Jong Woo Kim2,6, Min Wook Kim2, Youngae Jung3, Eunji Jang7, Seon-Jin Yoon8, Jungeun Kim7, Jihye Kim7, Jinho Seo9, Jeong-Ki Min5,10, Kyoung-Jin Oh2,6, Baek-Soo Han6,11, Won Kon Kim2,6, Kwang-Hee Bae2,6,12, Jaewhan Song13, Jaehoon Kim1, Yong-Min Huh14,7,12,15, Geum-Sook Hwang16,5, Eun-Woo Lee17, Sang Chul Lee17.
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 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.Entities:
Keywords: ELOVL5; FADS1; arachidonic acid; ferroptosis; lipid peroxidation
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Year: 2020 PMID： 33288688 PMCID： PMC7768719 DOI： 10.1073/pnas.2006828117
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779