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Persister cancer cells: Iron addiction and vulnerability to ferroptosis.
Mol. Cell 82, 728-740 (2022)
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 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.
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Publication type
Article: Journal article
Document type
Review
Keywords
Glutathione-peroxidase 4; Cystine/glutamate Antiporter; Promotes Ferroptosis; Lipid-peroxidation; Oxidative Stress; Stem-cells; Death; Inhibition; Mechanism; Complex
ISSN (print) / ISBN
1097-2765
e-ISSN
1097-4164
Journal
Molecular Cell
Quellenangaben
Volume: 82,
Issue: 4,
Pages: 728-740
Publisher
Elsevier
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Metabolism and Cell Death (MCD)
Grants
Else Kroner-Fresenius-Stiftung
Fondation Charles Defforey-Institut de France
Ligue contre le Cancer
Region Ile-de-France
National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network
Deutsche Forschungsgemeinschaft (DFG)
German Federal Ministry of Education and Research (BMBF) VIP+ program NEURO-PROTEKT
Ministry of Science and Higher Education of The Russian Federation
ERC under the European Union's Horizon 2020 research and innovation program
European Research Council (ERC) under the European Union
Fondation Charles Defforey-Institut de France
Ligue contre le Cancer
Region Ile-de-France
National Cancer Institute's Cancer Target Discovery and Development (CTD2) Network
Deutsche Forschungsgemeinschaft (DFG)
German Federal Ministry of Education and Research (BMBF) VIP+ program NEURO-PROTEKT
Ministry of Science and Higher Education of The Russian Federation
ERC under the European Union's Horizon 2020 research and innovation program
European Research Council (ERC) under the European Union