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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Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications
TL;DR: Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, was identified as a distinct phenomenon and named a decade ago as discussed by the authors , which has been implicated in a broad set of biological contexts, from development to aging, immunity, and cancer.
Journal ArticleDOI
Targeting ferroptosis as a vulnerability in cancer
Guang Lei,Li Zhuang,Boyi Gan +2 more
TL;DR: The current understanding of ferroptosis-inducing and ferroPTosis defence mechanisms is summarized, the roles and mechanisms of ferraptosis in tumour suppression and tumour immunity are dissected, and therapeutic strategies for targeting ferroaptosis in cancer are explored.
Journal ArticleDOI
Tumour fatty acid metabolism in the context of therapy resistance and obesity.
TL;DR: In this paper, the authors describe cellular fatty acid metabolic changes that are connected to therapy resistance and contextualize obesity-associated changes in host fatty acid metabolism that likely influence the local tumour microenvironment to further modify cancer cell behavior while simultaneously creating potential new vulnerabilities.
Journal ArticleDOI
Lipid Metabolism and Ferroptosis.
TL;DR: In this paper, the authors summarize the current knowledge of how various lipid metabolic pathways are associated with lipid peroxidation and ferroptosis and provide insight into treatment strategies for ferro-ptosis-related diseases.
Journal ArticleDOI
Ferroptosis at the intersection of lipid metabolism and cellular signaling.
TL;DR: In this paper , the authors provide a comprehensive analysis by focusing on how lipid metabolism impacts the initiation, propagation, and termination of phospholipid peroxidation, and how multiple signal transduction pathways communicate with ferroptosis via modulating lipid metabolism.
References
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Quantitative proteomic analyses reveal that GPX4 downregulation during myocardial infarction contributes to ferroptosis in cardiomyocytes
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Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1
Hironari Nishizawa,Mitsuyo Matsumoto,Tomohiko Shindo,Daisuke Saigusa,Hiroki Kato,Katsushi Suzuki,Masaki Sato,Yusho Ishii,Hiroaki Shimokawa,Kazuhiko Igarashi +9 more
TL;DR: It is proposed that BACH1 controls the threshold of ferroPTosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction.
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