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
More filters
Journal ArticleDOI
O-GlcNAcylation of ZEB1 facilitated mesenchymal pancreatic cancer cell ferroptosis
Xin Wang,Mengqi Liu,Yue Jack Chu,Yanfang Liu,Xiongfeng Cao,Hantian Zhang,Yaopeng Huang,Aihua Gong,Xiang Liao,Dongqing Wang,Haitao Zhu +10 more
TL;DR: A novel role of glycolipid metabolism and O-GlcNAcylation in mesenchymal cancer cells ferroptosis susceptibility is identified, which broaden the molecular mechanism of ferroPTosis and suggested a potential clinical therapeutic strategy for refractory tumors.
Journal ArticleDOI
Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer
TL;DR: The roles and functions of ferroPTosis and ferroptosis-related ncRNAs in GC tumorigenesis, development, and prognosis are summarized and the future research direction and challenges are prospected.
Journal ArticleDOI
Elucidating the Differences in Metal Toxicity by Quantitative Adverse Outcome Pathways.
TL;DR: This work provided a mechanistic explanation for the differences in metal toxicity where the strong bioaccumulation of Cu enables the newly accumulated Cu to reach the threshold that causes different adverse effects faster than Cd in zebrafish larvae, resulting in a higher toxicity of Cu than that of Cd.
Journal ArticleDOI
Ferroptosis-Driven Nanotherapeutics to Reverse Drug Resistance in Tumor Microenvironment.
TL;DR: Current trends of ferroptosis-driven nanotherapeutics to reverse drug resistance of tumors in anticancer fields at the intersection of cancer biology, materials science, and chemistry are elaborate.
Journal ArticleDOI
Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology: Progress and updates
TL;DR: Current research progress on the mechanism of ferroptosis, current inducers and inhibitors of ferrosynthesis, and the role of ferraptosis in GI tumors are reviewed to propose new methods for the treatment of such tumors.
References
More filters
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.
Related Papers (5)
FSP1 is a glutathione-independent ferroptosis suppressor
Sebastian Doll,Florencio Porto Freitas,Ron Shah,Maceler Aldrovandi,Milene Costa da Silva,Irina Ingold,Andrea Goya Grocin,Thamara Nishida Xavier da Silva,Elena Panzilius,Christina Scheel,André Mourão,Katalin Buday,Mami Sato,Jonas Wanninger,Thibaut Vignane,Vaishnavi Mohana,Markus Rehberg,Andrew Flatley,Aloys Schepers,Andreas Kurz,Daniel A. White,Markus Sauer,Michael Sattler,Edward W. Tate,Werner Schmitz,Almut Schulze,Valerie B. O'Donnell,Bettina Proneth,Grzegorz M. Popowicz,Derek A. Pratt,José Pedro Friedmann Angeli,Marcus Conrad +31 more
ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Sebastian Doll,Bettina Proneth,Yulia Y. Tyurina,Elena Panzilius,Sho Kobayashi,Irina Ingold,Martin Irmler,Johannes Beckers,Michaela Aichler,Axel Walch,Holger Prokisch,Dietrich Trümbach,Gaowei Mao,Feng Qu,Hülya Bayır,Joachim Füllekrug,Christina Scheel,Wolfgang Wurst,Joel A. Schick,Valerian E. Kagan,José Pedro Friedmann Angeli,Marcus Conrad +21 more
Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis
Valerian E. Kagan,Gaowei Mao,Feng Qu,José Pedro Friedmann Angeli,Sebastian Doll,Claudette M. St. Croix,Haider H. Dar,Bing Liu,Vladimir A. Tyurin,Vladimir B. Ritov,Alexandr A. Kapralov,Andrew A. Amoscato,Jianfei Jiang,Tamil S. Anthonymuthu,Dariush Mohammadyani,Qin Yang,Bettina Proneth,Judith Klein-Seetharaman,Simon C. Watkins,Ivet Bahar,Joel S. Greenberger,Rama K. Mallampalli,Brent R. Stockwell,Yulia Y. Tyurina,Marcus Conrad,Hülya Bayır +25 more