Iron and Cancer: More Ore to Be Mined

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2013 Apr 19

PMID 23594855

Citations 656

Authors

Suzy V Torti

Frank M Torti

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance.

DAprile S, Denaro S, Gervasi A, Vicario N, Parenti R Front Cell Dev Biol. 2025; 13:1535073.

PMID: 40078366 PMC: 11897528. DOI: 10.3389/fcell.2025.1535073.

The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches.

Catalano T, Selvaggi F, Cotellese R, Aceto G Cancers (Basel). 2025; 17(5).

PMID: 40075600 PMC: 11899472. DOI: 10.3390/cancers17050752.

An overview of the current evidences on the role of iron in colorectal cancer: a review.

Yousefi M, Masoudi A, Saberi Rounkian M, Mansouri M, Hojat B, Kaveh Samani M Front Oncol. 2025; 15:1499094.

PMID: 40066098 PMC: 11891053. DOI: 10.3389/fonc.2025.1499094.

Research Progress of Liver Cancer Recurrence Based on Energy Metabolism of Liver Cancer Stem Cells.

Wu M, Wang H, Wu X, Zeng H, Miao M, Song Y J Hepatocell Carcinoma. 2025; 12:467-480.

PMID: 40061164 PMC: 11887506. DOI: 10.2147/JHC.S500638.

Portable Cell Tracking Velocimetry for Quantification of Intracellular Fe Concentration of Blood Cells.

Tran L, Paz Gonzalez K, Choe H, Wu X, Strayer J, Iyer P Micromachines (Basel). 2025; 16(2).

PMID: 40047598 PMC: 11857336. DOI: 10.3390/mi16020126.

References

Terada N, Or R, Szepesi A, Lucas J, Gelfand E . Definition of the roles for iron and essential fatty acids in cell cycle progression of normal human T lymphocytes. Exp Cell Res. 1993; 204(2):260-7. DOI: 10.1006/excr.1993.1032. View

Osborne N, Gurrin L, Allen K, Constantine C, Delatycki M, McLaren C . HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010; 51(4):1311-8. PMC: 3815603. DOI: 10.1002/hep.23448. View

Zhang Y, Fan Y, Mei Z . NGAL and NGALR overexpression in human hepatocellular carcinoma toward a molecular prognostic classification. Cancer Epidemiol. 2012; 36(5):e294-9. DOI: 10.1016/j.canep.2012.05.012. View

Tsukamoto H . Iron regulation of hepatic macrophage TNFalpha expression. Free Radic Biol Med. 2002; 32(4):309-13. DOI: 10.1016/s0891-5849(01)00772-9. View

Netz D, Stith C, Stumpfig M, Kopf G, Vogel D, Genau H . Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes. Nat Chem Biol. 2011; 8(1):125-32. PMC: 3241888. DOI: 10.1038/nchembio.721. View

Boult J, Roberts K, Brookes M, Hughes S, Bury J, Cross S . Overexpression of cellular iron import proteins is associated with malignant progression of esophageal adenocarcinoma. Clin Cancer Res. 2008; 14(2):379-87. DOI: 10.1158/1078-0432.CCR-07-1054. View

Fukushima T, Kawabata H, Nakamura T, Iwao H, Nakajima A, Miki M . Iron chelation therapy with deferasirox induced complete remission in a patient with chemotherapy-resistant acute monocytic leukemia. Anticancer Res. 2011; 31(5):1741-4. View

Yang J, McNeish B, Butterfield C, Moses M . Lipocalin 2 is a novel regulator of angiogenesis in human breast cancer. FASEB J. 2012; 27(1):45-50. PMC: 3528324. DOI: 10.1096/fj.12-211730. View

Leung L, Radulovich N, Zhu C, Organ S, Bandarchi B, Pintilie M . Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma. PLoS One. 2012; 7(10):e46677. PMC: 3464270. DOI: 10.1371/journal.pone.0046677. View

10.

Hamazaki S, Okada S, Ebina Y, Fujioka M, MIDORIKAWA O . Nephrotoxicity of ferric nitrilotriacetate. An electron-microscopic and metabolic study. Am J Pathol. 1986; 123(2):343-50. PMC: 1888317. View

11.

Thierbach R, Schulz T, Isken F, Voigt A, Mietzner B, Drewes G . Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice. Hum Mol Genet. 2005; 14(24):3857-64. DOI: 10.1093/hmg/ddi410. View

12.

Peyssonnaux C, Zinkernagel A, Schuepbach R, Rankin E, Vaulont S, Haase V . Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest. 2007; 117(7):1926-32. PMC: 1884690. DOI: 10.1172/JCI31370. View

13.

Eberhard Y, McDermott S, Wang X, Gronda M, Venugopal A, Wood T . Chelation of intracellular iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and myeloma cells. Blood. 2009; 114(14):3064-73. DOI: 10.1182/blood-2009-03-209965. View

14.

Jiao Y, Wilkinson 4th J, Pietsch E, Buss J, Wang W, Planalp R . Iron chelation in the biological activity of curcumin. Free Radic Biol Med. 2006; 40(7):1152-60. DOI: 10.1016/j.freeradbiomed.2005.11.003. View

15.

Coffman L, Parsonage D, DAgostino Jr R, Torti F, Torti S . Regulatory effects of ferritin on angiogenesis. Proc Natl Acad Sci U S A. 2009; 106(2):570-5. PMC: 2626744. DOI: 10.1073/pnas.0812010106. View

16.

Pietrangelo A . Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology. 2010; 139(2):393-408, 408.e1-2. DOI: 10.1053/j.gastro.2010.06.013. View

17.

Schulz T, Thierbach R, Voigt A, Drewes G, Mietzner B, Steinberg P . Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited. J Biol Chem. 2005; 281(2):977-81. DOI: 10.1074/jbc.M511064200. View

18.

Knutson M . Steap proteins: implications for iron and copper metabolism. Nutr Rev. 2007; 65(7):335-40. DOI: 10.1111/j.1753-4887.2007.tb00311.x. View

19.

Daniels T, Bernabeu E, Rodriguez J, Patel S, Kozman M, Chiappetta D . The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta. 2011; 1820(3):291-317. PMC: 3500658. DOI: 10.1016/j.bbagen.2011.07.016. View

20.

Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch H, Strohmeyer G . Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med. 1985; 313(20):1256-62. DOI: 10.1056/NEJM198511143132004. View