Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer

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dc.contributor.authorLee, Ji-Yoonko
dc.contributor.authorNam, Misoko
dc.contributor.authorSon, Hye Youngko
dc.contributor.authorHyun, Kwangbeomko
dc.contributor.authorJang, Seo Youngko
dc.contributor.authorKim, Jong Wooko
dc.contributor.authorKim, Min Wookko
dc.contributor.authorJung, Youngaeko
dc.contributor.authorJang, Eunjiko
dc.contributor.authorYoon, Seon-Jinko
dc.contributor.authorKim, Jungeunko
dc.contributor.authorKim, Jihyeko
dc.contributor.authorSeo, Jinhoko
dc.contributor.authorMin, Jeong-Kiko
dc.contributor.authorOh, Kyoung-Jinko
dc.contributor.authorHan, K-Sooko
dc.contributor.authorKim, Won Konko
dc.contributor.authorBae, Kwang-Heeko
dc.contributor.authorSong, Jaewhanko
dc.contributor.authorKim, Jaehoonko
dc.contributor.authorHuh, Yong-Minko
dc.contributor.authorHwang, Geum-Sookko
dc.contributor.authorLee, Eun-Wooko
dc.contributor.authorLee, Sang Chulko
dc.date.accessioned2021-01-28T05:53:25Z-
dc.date.available2021-01-28T05:53:25Z-
dc.date.created2021-01-19-
dc.date.issued2020-12-
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.117, no.51, pp.32433 - 32442-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10203/280039-
dc.description.abstractFerroptosis 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.-
dc.languageEnglish-
dc.publisherNATL ACAD SCIENCES-
dc.titlePolyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer-
dc.typeArticle-
dc.identifier.wosid000601315200035-
dc.identifier.scopusid2-s2.0-85098227709-
dc.type.rimsART-
dc.citation.volume117-
dc.citation.issue51-
dc.citation.beginningpage32433-
dc.citation.endingpage32442-
dc.citation.publicationnamePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.identifier.doi10.1073/pnas.2006828117-
dc.contributor.localauthorKim, Jaehoon-
dc.contributor.nonIdAuthorNam, Miso-
dc.contributor.nonIdAuthorSon, Hye Young-
dc.contributor.nonIdAuthorJang, Seo Young-
dc.contributor.nonIdAuthorKim, Jong Woo-
dc.contributor.nonIdAuthorKim, Min Wook-
dc.contributor.nonIdAuthorJung, Youngae-
dc.contributor.nonIdAuthorJang, Eunji-
dc.contributor.nonIdAuthorYoon, Seon-Jin-
dc.contributor.nonIdAuthorKim, Jungeun-
dc.contributor.nonIdAuthorKim, Jihye-
dc.contributor.nonIdAuthorSeo, Jinho-
dc.contributor.nonIdAuthorMin, Jeong-Ki-
dc.contributor.nonIdAuthorOh, Kyoung-Jin-
dc.contributor.nonIdAuthorHan, K-Soo-
dc.contributor.nonIdAuthorKim, Won Kon-
dc.contributor.nonIdAuthorBae, Kwang-Hee-
dc.contributor.nonIdAuthorSong, Jaewhan-
dc.contributor.nonIdAuthorHuh, Yong-Min-
dc.contributor.nonIdAuthorHwang, Geum-Sook-
dc.contributor.nonIdAuthorLee, Eun-Woo-
dc.contributor.nonIdAuthorLee, Sang Chul-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorferroptosis-
dc.subject.keywordAuthorlipid peroxidation-
dc.subject.keywordAuthorELOVL5-
dc.subject.keywordAuthorFADS1-
dc.subject.keywordAuthorarachidonic acid-
dc.subject.keywordPlusCELL-DEATH-
dc.subject.keywordPlusMETABOLISM-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusRESISTANCE-
dc.subject.keywordPlusACSL4-
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