Persister cancer cells: Iron addiction and vulnerability to ferroptosis.
Persister cancer cells: Iron addiction and vulnerability to ferroptosis.
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DOI：
10.1016/j.molcel.2021.12.001
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发表时间：
2022-02-17
期刊：
影响因子：
16
通讯作者：
Conrad, Marcus
中科院分区：
文献类型：
--
作者：
Rodriguez, Raphae;Schreiber, Stuart L.;Conrad, Marcus
铁死亡是一种独特的非凋亡性细胞死亡，由过度氧化磷脂的无限制发生引起，这是受铁介导的致命氧自由基产生的影响。这种细胞死亡模式已经在许多生物中被检测到，包括在哺乳动物中，它可以被用作对抗病原体的防御机制，甚至被T细胞利用来使肿瘤细胞敏感，从而有效杀死。相反，铁下垂被认为是促进退行性疾病的主要细胞死亡机制之一。新出现的证据表明，铁下垂是某些癌症的易感因素。在这里，我们批判性地回顾了最近的进展，将去分化和持续性癌细胞的铁凋亡脆弱性与这些细胞对铁的依赖性联系起来，铁是小分子干预的潜在致命弱点。我们提供了一个依赖于铁的机制，有助于癌细胞的持续状态，以及如何利用这种依赖性的治疗效益的观点。Rodriguez等人讨论了铁如何使细胞获得耐药持续性癌症状态，以及这种成瘾如何使铁下垂高度易感。因此，这一特征为识别铁下垂敏感性的新预测因子提供了前所未有的机会，并为开发下一代治疗方法提供了基础。
Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it can be used as a defense mechanism against pathogens or even harnessed by T cells to sensitize tumor cells toward effective killing. Conversely, ferroptosis is considered as one of the main cell death mechanisms promoting degenerative diseases. Emerging evidence suggests that ferroptosis represents a vulnerability in certain cancers. Here, we critically review recent advances linking ferroptosis vulnerabilities of dedifferentiating and persister cancer cells to the dependency of these cells on iron, a potential Achilles’ heel for small molecule intervention. We provide a perspective on the mechanisms reliant on iron that contribute to the persister cancer cell state and how this dependency may be exploited for therapeutic benefits. Rodriguez et al. discuss how iron allows cells to acquire a drug-tolerant persister cancer state and how this addiction confers a high vulnerability to ferroptosis. This feature therefore opens up unprecedented opportunities to identify new predictors of ferroptosis sensitivity and provides the basis for the development of next-generation therapeutics.
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DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
2.7
作者：
Eaton JK;Furst L;Cai LL;Viswanathan VS;Schreiber SL
通讯作者：
Schreiber SL
影响因子：
56.9
作者：
Chen, Mark S.;White, M. Christina
通讯作者：
White, M. Christina
影响因子：
4
作者：
Dixon SJ;Winter GE;Musavi LS;Lee ED;Snijder B;Rebsamen M;Superti-Furga G;Stockwell BR
通讯作者：
Stockwell BR