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Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It

Institut Necker-Enfants Malades (INEM), Inserm U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, F-75993 Paris, France
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Guangzhou 510120, China
Authors to whom correspondence should be addressed.
Academic Editor: George Simos
Cells 2021, 10(11), 2981;
Received: 29 September 2021 / Revised: 29 October 2021 / Accepted: 29 October 2021 / Published: 2 November 2021
Cancer stem cells (CSCs) are a distinct subpopulation of tumor cells with stem cell-like features. Able to initiate and sustain tumor growth and mostly resistant to anti-cancer therapies, they are thought responsible for tumor recurrence and metastasis. Recent accumulated evidence supports that iron metabolism with the recent discovery of ferroptosis constitutes a promising new lead in the field of anti-CSC therapeutic strategies. Indeed, iron uptake, efflux, storage and regulation pathways are all over-engaged in the tumor microenvironment suggesting that the reprogramming of iron metabolism is a crucial occurrence in tumor cell survival. In particular, recent studies have highlighted the importance of iron metabolism in the maintenance of CSCs. Furthermore, the high concentration of iron found in CSCs, as compared to non-CSCs, underlines their iron addiction. In line with this, if iron is an essential macronutrient that is nevertheless highly reactive, it represents their Achilles’ heel by inducing ferroptosis cell death and therefore providing opportunities to target CSCs. In this review, we first summarize our current understanding of iron metabolism and its regulation in CSCs. Then, we provide an overview of the current knowledge of ferroptosis and discuss the role of autophagy in the (regulation of) ferroptotic pathways. Finally, we discuss the potential therapeutic strategies that could be used for inducing ferroptosis in CSCs to treat cancer. View Full-Text
Keywords: iron metabolism; ferroptosis; autophagy; cancer stem cells iron metabolism; ferroptosis; autophagy; cancer stem cells
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MDPI and ACS Style

Cosialls, E.; El Hage, R.; Dos Santos, L.; Gong, C.; Mehrpour, M.; Hamaï, A. Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It. Cells 2021, 10, 2981.

AMA Style

Cosialls E, El Hage R, Dos Santos L, Gong C, Mehrpour M, Hamaï A. Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It. Cells. 2021; 10(11):2981.

Chicago/Turabian Style

Cosialls, Emma, Rima El Hage, Leïla Dos Santos, Chang Gong, Maryam Mehrpour, and Ahmed Hamaï. 2021. "Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It" Cells 10, no. 11: 2981.

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