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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Additional file 8 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
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Additional file 5 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
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Additional file 2 of Identification of immune subtypes of Ph-neg B-ALL with ferroptosis related genes and the potential implementation of Sorafenib
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Additional file 7 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
Yao, J., Chen, X., Liu, X., Li, R., Zhou, X., & Qu, Y.-Q. (2021) · Figshare · doi:10.6084/m9.figshare.14906071
Additional file 6 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
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Additional file 1 of FTH promotes the proliferation and renders the HCC cells specifically resist to ferroptosis by maintaining iron homeostasis
Hu, W., Zhou, C., Jing, Q., Li, Y., Yang, J., Yang, C., Wang, L., Hu, J., Li, H., Wang, H., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17704597
Additional file 2 of Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Luo, G., Wang, L., Zheng, Z., Gao, B., & Lei, C. (2023) · Figshare · doi:10.6084/m9.figshare.22826719
Additional file 3 of FTH promotes the proliferation and renders the HCC cells specifically resist to ferroptosis by maintaining iron homeostasis
Hu, W., Zhou, C., Jing, Q., Li, Y., Yang, J., Yang, C., Wang, L., Hu, J., Li, H., Wang, H., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17704603
Additional file 5 of Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Luo, G., Wang, L., Zheng, Z., Gao, B., & Lei, C. (2023) · Figshare · doi:10.6084/m9.figshare.22826728
Additional file 4 of FTH promotes the proliferation and renders the HCC cells specifically resist to ferroptosis by maintaining iron homeostasis
Hu, W., Zhou, C., Jing, Q., Li, Y., Yang, J., Yang, C., Wang, L., Hu, J., Li, H., Wang, H., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17704606
Additional file 3 of The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma
Tang, B., Zhu, J., Li, J., Fan, K., Gao, Y., Cheng, S., Kong, C., Zheng, L., Wu, F., Weng, Q., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13161696
Additional file 6 of Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Luo, G., Wang, L., Zheng, Z., Gao, B., & Lei, C. (2023) · Figshare · doi:10.6084/m9.figshare.22826731
Additional file 4 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558540
Additional file 7 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558549
Additional file 9 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558555
Additional file 4 of Inhibition of CISD2 promotes ferroptosis through ferritinophagy-mediated ferritin turnover and regulation of p62–Keap1–NRF2 pathway
Li, Y., Xu, B., Ren, X., Wang, L., Xu, Y., Zhao, Y., Yang, C., Yuan, C., Li, H., Tong, X., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21256983
Additional file 1 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558531
Additional file 10 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558558
Additional file 5 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558543
Additional file 4 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
Yao, J., Chen, X., Liu, X., Li, R., Zhou, X., & Qu, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14906062
Additional file 1 of Identification of immune subtypes of Ph-neg B-ALL with ferroptosis related genes and the potential implementation of Sorafenib
Hong, Y., Zhang, L., Tian, X., Xiang, X., Yu, Y., Zeng, Z., Cao, Y., Chen, S., & 孙爱宁 (2021) · Figshare · doi:10.6084/m9.figshare.17204923
Additional file 5 of The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma
Tang, B., Zhu, J., Li, J., Fan, K., Gao, Y., Cheng, S., Kong, C., Zheng, L., Wu, F., Weng, Q., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13161702
Additional file 3 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558537
Additional file 2 of The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma
Tang, B., Zhu, J., Li, J., Fan, K., Gao, Y., Cheng, S., Kong, C., Zheng, L., Wu, F., Weng, Q., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13161693
Additional file 11 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558561
Additional file 12 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558564
Additional file 2 of FTH promotes the proliferation and renders the HCC cells specifically resist to ferroptosis by maintaining iron homeostasis
Hu, W., Zhou, C., Jing, Q., Li, Y., Yang, J., Yang, C., Wang, L., Hu, J., Li, H., Wang, H., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17704600
Additional file 2 of Inhibition of CISD2 promotes ferroptosis through ferritinophagy-mediated ferritin turnover and regulation of p62–Keap1–NRF2 pathway
Li, Y., Xu, B., Ren, X., Wang, L., Xu, Y., Zhao, Y., Yang, C., Yuan, C., Li, H., Tong, X., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21256977
Additional file 7 of Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Luo, G., Wang, L., Zheng, Z., Gao, B., & Lei, C. (2023) · Figshare · doi:10.6084/m9.figshare.22826734
Additional file 1 of UBE2C promotes the proliferation of acute myeloid leukemia cells through PI3K/AKT activation
Wang, L., Zhao, S., Wang, Y., Liu, J., & Wang, X. (2024) · Figshare · doi:10.6084/m9.figshare.25649379
Additional file 3 of Inhibition of CISD2 promotes ferroptosis through ferritinophagy-mediated ferritin turnover and regulation of p62–Keap1–NRF2 pathway
Li, Y., Xu, B., Ren, X., Wang, L., Xu, Y., Zhao, Y., Yang, C., Yuan, C., Li, H., Tong, X., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21256980
Additional file 1 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
Yao, J., Chen, X., Liu, X., Li, R., Zhou, X., & Qu, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14906053
Additional file 1 of Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Luo, G., Wang, L., Zheng, Z., Gao, B., & Lei, C. (2023) · Figshare · doi:10.6084/m9.figshare.22826716
Additional file 3 of Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Luo, G., Wang, L., Zheng, Z., Gao, B., & Lei, C. (2023) · Figshare · doi:10.6084/m9.figshare.22826722
Additional file 8 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558552
Additional file 4 of Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Luo, G., Wang, L., Zheng, Z., Gao, B., & Lei, C. (2023) · Figshare · doi:10.6084/m9.figshare.22826725
Additional file 6 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558546
Additional file 4 of The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma
Tang, B., Zhu, J., Li, J., Fan, K., Gao, Y., Cheng, S., Kong, C., Zheng, L., Wu, F., Weng, Q., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13161699
Additional file 3 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
Yao, J., Chen, X., Liu, X., Li, R., Zhou, X., & Qu, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14906059
Additional file 1 of Inhibition of CISD2 promotes ferroptosis through ferritinophagy-mediated ferritin turnover and regulation of p62–Keap1–NRF2 pathway
Li, Y., Xu, B., Ren, X., Wang, L., Xu, Y., Zhao, Y., Yang, C., Yuan, C., Li, H., Tong, X., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21256974
Additional file 2 of Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma
Yao, J., Chen, X., Liu, X., Li, R., Zhou, X., & Qu, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14906056
Additional file 2 of High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Tang, Y., Ge, S., Zheng, X., & Zheng, J. (2024) · Figshare · doi:10.6084/m9.figshare.26558534
Additional file 1 of Ginsenoside compound K induces ferroptosis via the FOXO pathway in liver cancer cells
Chen, J., Wang, Z., Fu, J., Cai, Y., Cheng, H., Cui, X., Sun, M., Liu, M., & Zhang, X. (2024) · Figshare · doi:10.6084/m9.figshare.26711942
Tumor responsive nanoplatforms for TME modulation: From extracellular matrix to intracellular organelles
Shu, H., Sia, C. S., Tiang, S. S. L., Goh, B.-H., Low, Y. J., Tey, B. T., & Low, L. E. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.108211
Targeted delivery and controlled release of deferasirox for melanoma therapy
Su, X., Zhao, W., Wang, L., Song, P., Wang, X., Jin, X., & Zhang, H. (2026) · iScience · doi:10.1016/j.isci.2026.115303
Ferroptosis as a novel targeted therapy in gynecological malignant tumors
Yu, C., Li, Y., Fu, Y., Yang, R., Nakevska, Z., Kumar, P. P., Tong, A. Y., Yang, N., Liu, D., Chen, C., et al. (2026) · Discover Oncology · doi:10.1007/s12672-026-04686-x
“Research has shown that cancer cells have a higher iron requirement for survival compared to normal cells [17].”
Rôle de l'autophagie dans l'émergence des cellules souches cancéreuses : implication du métabolisme
El-Hout, M. (2019) · theses.fr (ABES) · doi:10.70675/881cf980z01caz4a56z8a81zdcebe1247536

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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