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The Hallmarks of Ferroptosis
Ferroptosis is a nonapoptotic, iron-dependent form of cell death that can be activated in cancer cells by natural stimuli and synthetic agents. Three essential hallmarks define ferroptosis, namely: the loss of lipid peroxide repair capacity by the phospholipid hydroperoxidase GPX4, the availability...
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Published in: | Annual review of cancer biology 2019-03, Vol.3 (1), p.35-54 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Request full text |
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Summary: | Ferroptosis is a nonapoptotic, iron-dependent form of cell death that can be activated in cancer cells by natural stimuli and synthetic agents. Three essential hallmarks define ferroptosis, namely: the loss of lipid peroxide repair capacity by the phospholipid hydroperoxidase GPX4, the availability of redox-active iron, and oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids. Several processes including RAS MAPK signaling, amino acid and iron metabolism, ferritinophagy, epithelial-to-mesenchymal transition, cell adhesion, and mevalonate and phospholipid biosynthesis can modulate susceptibility to ferroptosis. Ferroptosis sensitivity is also governed by p53 and KEAP1 NRF2 activity, linking ferroptosis to the function of key tumor suppressor pathways. Together these findings highlight the role of ferroptosis as an emerging concept in cancer biology and an attractive target for precision cancer medicine discovery. |
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ISSN: | 2472-3428 2472-3428 |
DOI: | 10.1146/annurev-cancerbio-030518-055844 |