Iron and cancer: more ore to be mined
Open accessAbstract
Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.
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Iron goes through lysosomal/endosomal membrane protein DMT1 for intracellular use.
“Additionally, lysosome is one of the most Fe(II)-rich organella [41], and iron should go through lysosomal/endosomal membrane protein (divalent metal transporter 1: DMT1) for intracellular use [69].”
From Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium (2020) · cites this paper as [69]
The Clinical and population-based studies section says DMT1 facilitates the movement of ferrous iron out of endosomes into a pool from which it reaches intracellular destinations. It does not establish transport across lysosomal membranes or that all iron must pass through DMT1 for intracellular use. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCancer cells stockpile intracellular iron through deregulating iron homeostasis mechanisms.
“Further corroborating the link between intracellular iron stores and proliferation, cancer cells are known to stockpile intracellular iron through deregulating iron homeostasis mechanisms (Torti and Torti, 2013).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Torti and Torti, 2013
Labile Fe2+ reacting with H2O2 can produce the harmful hydroxyl radical through the Fenton reaction.
“When labile Fe2+ in these pools reacts with H2O2, it can generate the damaging hydroxyl radical (•OH) via the Fenton reaction21”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [21]
Pharmacological ascorbate might avoid the narrow therapeutic window of pro-oxidant therapy by using two common cancer features: more labile transition metals, especially iron, and greater dependence on glucose uptake and glycolysis.
“we propose that pharmacological ascorbate can potentially circumvent this problem by exploring two common features of cancer cells: their increased levels of labile transition metals, especially iron21, and their increased reliance on glucose uptake and glycolysis22.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [21]
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- [129]Tsukamoto H Iron regulation of hepatic macrophage TNFalpha expression Free Radic. Biol. Med 2002 32 309 313 11841920
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- Authors
- Torti, S. V., & Torti, F. M.
- Affiliations
- UConn Health (US)
- Corresponding author
- Torti, Suzy V.
- Torti, Frank M.
- Venue
- Nature Reviews Cancer
- Published
- 2013-04-18
- Volume
- 13
- Issue
- 5
- Pages
- 342-355
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC4036554
- OpenAlex
- W2062107099
- Cited by
- 1,621
- References
- 193
- Citations by year
- 2026: 111 · 2025: 148 · 2024: 156 · 2023: 176 · 2022: 177 · 2021: 174 · 2020: 137 · 2019: 131 · 2018: 109 · 2017: 99 · 2016: 82 · 2015: 65 · 2014: 38 · 2013: 16
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OpenCommons at University of Connecticut (University of Connecticut) (submittedVersion)
- OpenCommons - UConn (University of Connecticut) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA171101)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071892)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- iron metabolism, cancer, iron efflux, iron storage, tumor microenvironment, metastasis, hypoxia-inducible factor, Wnt signaling, redox cycling, free radicals, tumor growth
- MeSH terms
- Animals, Antineoplastic Agents, Cell Cycle, DNA, Humans, Iron, Iron Chelating Agents, Neoplasms, Signal Transduction, Cell Hypoxia, Iron-Binding Proteins, Metabolic Networks and Pathways, Tumor Microenvironment
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