Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer.
Ji Yoon Lee,Ji Yoon Lee,Miso Nam,Hye Young Son,Kwangbeom Hyun,Seo Young Jang,Jong Woo Kim,Min Wook Kim,Youngae Jung,Eunji Jang,Seon Jin Yoon,Jung-Eun Kim,Jihye Kim,Jin-Ho Seo,Jeong Ki Min,Kyoung Jin Oh,Baek Soo Han,Won Kon Kim,Kwang-Hee Bae,Kwang-Hee Bae,Jaewhan Song,Jae-Hoon Kim,Yong Min Huh,Geum-Sook Hwang,Eun-Woo Lee,Sang Chul Lee +25 more
TLDR
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, and the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroPTosis.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.read more
Citations
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FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication
TL;DR: In this paper , the authors show that hepatitis C virus is restricted by an iron-dependent mechanism resembling the one triggering ferroptosis, an irondependent form of non-apoptotic cell death, and mediated by the non-canonical desaturation of oleate to Mead acid and other highly unsaturated fatty acids by fatty acid desaturase 2 (FADS2).
Journal ArticleDOI
Upregulated aminoacyl-tRNA biosynthesis contributes to metabolic dysregulation in gastric cancer
Xiaoling Gao,Rui Guo,Yonghong Li,Guolan Kang,Yu Wu,Jia Cheng,Jing Jia,Wanxia Wang,Zhenhao Li,Anqi Wang,Hui Xu,Yanjuan Jia,Yuanting Li,Xiaoming Qi,Zhenhong Wei,Chaojun Wei +15 more
TL;DR: In this article, a novel therapeutic strategy for gastric cancer was proposed that involves targeting the aminoacyl-tRNA biosynthesis pathway, which was consistent with the results of transcriptome analysis.
Journal ArticleDOI
Metabolic Regulation of Ferroptosis in Cancer
TL;DR: In this paper, the authors present an update of the mechanisms underlying diverse metabolic pathways that can regulate ferroptosis in cancer, including iron, cyst(e)ine, glutathione, and lipid metabolism.
Journal ArticleDOI
Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease
TL;DR: Ferroptosis is a form of regulated cell death (RCD) that is typically accompanied by iron accumulation and lipid peroxidation, and it is involved in the progression of multiple diseases and could be a novel therapeutic target in the future.
Journal ArticleDOI
Ferroptosis in hematological malignancies and its potential network with abnormal tumor metabolism.
TL;DR: In this paper , the potential interactions between ferroptosis and abnormal tumor metabolism, with a special focus on systematic researches in hematological malignancies, are discussed.
References
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Journal ArticleDOI
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Scott J. Dixon,Kathryn M. Lemberg,Michael R. Lamprecht,Rachid Skouta,Eleina M. Zaitsev,Caroline E Gleason,Darpan N Patel,Andras J. Bauer,Alexandra M. Cantley,Wan Seok Yang,Barclay Morrison,Brent R. Stockwell,Brent R. Stockwell +12 more
TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
Journal ArticleDOI
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Jordi Barretina,Giordano Caponigro,Nicolas Stransky,Kavitha Venkatesan,Adam A. Margolin,Adam A. Margolin,Sungjoon Kim,Christine D. Wilson,Joseph Lehar,Gregory V. Kryukov,Dmitriy Sonkin,Anupama Reddy,Manway Liu,Lauren Murray,Michael F. Berger,Michael F. Berger,John Monahan,Paula Morais,Jodi Meltzer,Adam Korejwa,Judit Jané-Valbuena,Judit Jané-Valbuena,Felipa A. Mapa,Joseph Thibault,Eva Bric-Furlong,Pichai Raman,Aaron Shipway,Ingo H. Engels,Jill Cheng,Guoying K. Yu,Jianjun Yu,Peter Aspesi,Melanie de Silva,Kalpana Jagtap,Michael D. Jones,Li Wang,Charlie Hatton,Emanuele Palescandolo,Supriya Gupta,Scott Mahan,Carrie Sougnez,Robert C. Onofrio,Ted Liefeld,Laura E. MacConaill,Wendy Winckler,Michael R. Reich,Nanxin Li,Jill P. Mesirov,Stacey Gabriel,Gad Getz,Kristin G. Ardlie,Vivien W. Chan,Vic E. Myer,Barbara L. Weber,Jeffrey A. Porter,Markus Warmuth,Peter Finan,Jennifer L. Harris,Matthew Meyerson,Matthew Meyerson,Todd R. Golub,Michael Morrissey,William R. Sellers,Robert Schlegel,Levi A. Garraway,Levi A. Garraway +65 more
TL;DR: The results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents and the generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of ‘personalized’ therapeutic regimens.
Journal ArticleDOI
Inferring tumour purity and stromal and immune cell admixture from expression data
Kosuke Yoshihara,Maria Shahmoradgoli,Emmanuel Martinez,Rahulsimham Vegesna,Hoon Kim,Wandaliz Torres-Garcia,Victor Trevino,Hui Shen,Peter W. Laird,Douglas A. Levine,Scott L. Carter,Gad Getz,Katherine Stemke-Hale,Gordon B. Mills,Roel G.W. Verhaak +14 more
TL;DR: A method that uses gene expression signatures to infer the fraction of stromal and immune cells in tumour samples and prediction accuracy is corroborated using 3,809 transcriptional profiles available elsewhere in the public domain.
Journal ArticleDOI
Regulation of Ferroptotic Cancer Cell Death by GPX4
Wan Seok Yang,Rohitha SriRamaratnam,Matthew Welsch,Kenichi Shimada,Rachid Skouta,Vasanthi S. Viswanathan,Vasanthi S. Viswanathan,Jaime H. Cheah,Paul A. Clemons,Alykhan F. Shamji,Clary B. Clish,Lewis M. Brown,Albert W. Girotti,Virginia W. Cornish,Stuart L. Schreiber,Brent R. Stockwell +15 more
TL;DR: Targeted metabolomic profiling and chemoproteomics revealed that GPX4 is an essential regulator of ferroptotic cancer cell death and sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPx4-regulated ferroPTosis.
Journal ArticleDOI
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Brent R. Stockwell,José Pedro Friedmann Angeli,Hülya Bayır,Ashley I. Bush,Marcus Conrad,Scott J. Dixon,Simone Fulda,Susan Gascon,Stavroula K. Hatzios,Valerian E. Kagan,Kay Noel,Xuejun Jiang,Andreas Linkermann,Maureen E. Murphy,Michael Overholtzer,Atsushi Oyagi,Gabriela Carolina Pagnussat,Jason Park,Qitao Ran,Craig S. Rosenfeld,Konstantin Salnikow,Daolin Tang,Daolin Tang,Frank M. Torti,Suzy V. Torti,Shinya Toyokuni,K. A. Woerpel,Donna D. Zhang +27 more
TL;DR: The mechanisms underlying ferroptosis are reviewed, connections to other areas of biology and medicine are highlighted, and tools and guidelines for studying this emerging form of regulated cell death are recommended.
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