Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It
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...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/2981 |
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| author | Emma Cosialls Rima El Hage Leïla Dos Santos Chang Gong Maryam Mehrpour Ahmed Hamaï |
| author_facet | Emma Cosialls Rima El Hage Leïla Dos Santos Chang Gong Maryam Mehrpour Ahmed Hamaï |
| author_sort | Emma Cosialls |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T05:37:15Z |
| format | Article |
| id | doaj.art-4a553e184e75440a9d11b2a53d851e8b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:15Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4a553e184e75440a9d11b2a53d851e8b2023-11-22T22:49:37ZengMDPI AGCells2073-44092021-11-011011298110.3390/cells10112981Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” ItEmma Cosialls0Rima El Hage1Leïla Dos Santos2Chang Gong3Maryam Mehrpour4Ahmed Hamaï5Institut Necker-Enfants Malades (INEM), Inserm U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, F-75993 Paris, FranceInstitut Necker-Enfants Malades (INEM), Inserm U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, F-75993 Paris, FranceInstitut Necker-Enfants Malades (INEM), Inserm U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, F-75993 Paris, FranceBreast Tumor Center, Sun Yat-sen Memorial Hospital, Guangzhou 510120, ChinaInstitut Necker-Enfants Malades (INEM), Inserm U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, F-75993 Paris, FranceInstitut Necker-Enfants Malades (INEM), Inserm U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, F-75993 Paris, FranceCancer 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.https://www.mdpi.com/2073-4409/10/11/2981iron metabolismferroptosisautophagycancer stem cells |
| spellingShingle | Emma Cosialls Rima El Hage Leïla Dos Santos Chang Gong Maryam Mehrpour Ahmed Hamaï Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It Cells iron metabolism ferroptosis autophagy cancer stem cells |
| title | Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It |
| title_full | Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It |
| title_fullStr | Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It |
| title_full_unstemmed | Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It |
| title_short | Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It |
| title_sort | ferroptosis cancer stem cells rely on iron until to die for it |
| topic | iron metabolism ferroptosis autophagy cancer stem cells |
| url | https://www.mdpi.com/2073-4409/10/11/2981 |
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