Cited by 515Iron Metabolism and DisordersFerroptosis and cancer prognosisTrace Elements in Health

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Iron and cancer: recent insights

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Manz, David H., Blanchette, Nicole L., Paul, Bibbin T., Torti, Frank M., Torti, Suzy V.·2016·Annals of the New York Academy of Sciences

DOI 10.1111/nyas.13008PMC PMC4870095

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Abstract

Iron is an essential dietary element. However, the ability of iron to cycle between oxidized and reduced forms also renders it capable of contributing to free radical formation, which can have deleterious effects, including promutagenic effects that can potentiate tumor formation. Dysregulation of iron metabolism can increase cancer risk and promote tumor growth. Cancer cells exhibit an enhanced dependence on iron relative to their normal counterparts, a phenomenon we have termed iron addiction. Work conducted in the past few years has revealed new cellular processes and mechanisms that deepen our understanding of the link between iron and cancer. Control of iron efflux through the combined action of ferroportin, an iron efflux pump, and its regulator hepcidin appears to play an important role in tumorigenesis. Ferroptosis is a form of iron‐dependent cell death involving the production of reactive oxygen species. Specific mechanisms involved in ferroptosis, including depletion of glutathione and inhibition of glutathione peroxidase 4, have been uncovered. Ferritinophagy is a newly identified mechanism for degradation of the iron storage protein ferritin. Perturbations of mechanisms that control transcripts encoding proteins that regulate iron have been observed in cancer cells, including differences in miRNA, methylation, and acetylation. These new insights may ultimately provide new therapeutic opportunities for treating cancer.

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Ferroptosis: mechanisms, biology and role in disease
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“Cancer cells have been shown to have increased iron requirements for survival in comparison to normal cells [24].”
Background
Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
Rochette, L., Dogon, G., Rigal, E., Zeller, M., Cottin, Y., & Vergely, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010449 · Cited by 966
“Several modulators of ferroptosis have been identified through the study of ferroptotic mechanisms [52].”
Background
Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies
Zhou, Q., Meng, Y., Li, D., Yao, L., Le, J., Liu, Y., Sun, Y., Zeng, F., Chen, X., & Deng, G. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01769-5 · Cited by 1,056
“11,368,369 Intriguingly, mesenchymal and dedifferentiated cancer cells, which are usually resistant to apoptosis and traditional therapies, are exquisitely vulnerable to ferropto-sis.”
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Authors: Manz, D. H., Blanchette, N. L., Paul, B. T., Torti, F. M., & Torti, S. V.
Affiliations: Department of Molecular Biology and Biophysics
UConn Health (US)
Corresponding author: Torti, Suzy V.
ORCID: Torti, Frank M.
Torti, Suzy V.
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 2016-02-18
Volume: 1368
Issue: 1
Pages: 149-161
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1111/nyas.13008
PMC: PMC4870095
OpenAlex: W2275201610
Cited by: 507
References: 121
Citations by year: 2026: 24 · 2025: 49 · 2024: 69 · 2023: 78 · 2022: 66 · 2021: 77 · 2020: 46 · 2019: 43 · 2018: 31 · 2017: 14 · 2016: 10
FWCI: 4.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: S.V.T (CA188025)
F.M.T (CA171101)
D.H.M. (DE021989)
U.S. National Institutes of Health
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: iron metabolism, cancer, ferroptosis, ferroportin, hepcidin, iron efflux, reactive oxygen species, glutathione depletion, GPX4, ferritinophagy, ferritin degradation, tumor microenvironment, epigenetic regulation, microRNA, DNA methylation, histone acetylation, cancer therapy
MeSH terms: Ferroportin, Animals, Humans, Iron, Neoplasms, Reactive Oxygen Species, Iron Overload, Cation Transport Proteins

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