铁下垂的标志

IF 4.7 2区医学 Q1 ONCOLOGY

Annual Review of Cancer Biology-Series Pub Date : 2019-03-04 DOI:10.1146/ANNUREV-CANCERBIO-030518-055844

S. Dixon, B. Stockwell

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引用次数: 338

摘要

脱铁症是一种非凋亡性铁依赖性细胞死亡，可在癌症细胞中通过自然刺激和合成剂激活。定义脱铁性贫血的三个基本特征，即：磷脂氢过氧化物酶GPX4失去脂质过氧化物修复能力，氧化还原活性铁的可用性，以及含有多不饱和脂肪酸（PUFA）的磷脂的氧化。包括RAS/MAPK信号传导、氨基酸和铁代谢、铁蛋白吞噬、上皮-间充质转化、细胞粘附以及甲羟戊酸和磷脂生物合成在内的几个过程可以调节对脱铁性贫血的易感性。脱铁敏感性还受p53和KEAP1/NRF2活性的控制，将脱铁与关键肿瘤抑制途径的功能联系起来。总之，这些发现突出了脱铁症作为癌症生物学中一个新兴概念和癌症医学精确发现的一个有吸引力的靶点的作用。

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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 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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来源期刊

Annual Review of Cancer Biology-Series Medicine-Oncology

CiteScore

14.50

自引率

1.30%

发文量

期刊介绍： The Annual Review of Cancer Biology offers comprehensive reviews on various topics within cancer research, covering pivotal and emerging areas in the field. As our understanding of cancer's fundamental mechanisms deepens and more findings transition into targeted clinical treatments, the journal is structured around three main themes: Cancer Cell Biology, Tumorigenesis and Cancer Progression, and Translational Cancer Science. The current volume of this journal has transitioned from gated to open access through Annual Reviews' Subscribe to Open program, ensuring all articles are published under a CC BY license.