The Hallmarks of Ferroptosis
The Hallmarks of Ferroptosis
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DOI：
10.1146/annurev-cancerbio-030518-055844
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Stockwell, Brent R.
中科院分区：
文献类型：
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作者：
Dixon, Scott J.;Stockwell, Brent R.
铁死亡是一种非凋亡、铁依赖性细胞死亡形式，可以通过自然刺激和合成药物在癌细胞中激活。铁死亡由三个基本特征定义，即：磷脂氢过氧化物酶 GPX4 导致的脂质过氧化物修复能力丧失、氧化还原活性铁的可用性以及含多不饱和脂肪酸 (PUFA) 的磷脂的氧化。包括 RAS/MAPK 信号传导、氨基酸和铁代谢、铁蛋白自噬、上皮间质转化、细胞粘附以及甲羟戊酸和磷脂生物合成在内的多个过程可以调节铁死亡的易感性。铁死亡敏感性还受 p53 和 KEAP1/NRF2 活性的控制，将铁死亡与关键肿瘤抑制途径的功能联系起来。这些发现共同强调了铁死亡作为癌症生物学中的新兴概念和精准癌症医学发现的有吸引力的目标的作用。
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 redoxactive 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.