A promising new approach to cancer therapy: Targeting iron metabolism in cancer stem cells. (December 2018)

• Record Type: Journal Article
• Authors: El Hout, Mouradi; Dos Santos, Leïla; Hamaï, Ahmed; Mehrpour, Maryam
• Is Part Of: Seminars in cancer biology. Volume 53(2018)
• Page Start: 125
• Page End: 138
• Publication Date: 2018-12
• Subjects: 15-LOX 15-lipoxygenase -- ALKBH5 AlkB homologue 5 -- ACSL4 acyl-CoA synthetase long chain family member 4 -- CP ceruloplasmin -- EMT epithelial–mesenchymal transition -- DMT1 divalent metal [ion] transport 1 -- DPP dipeptidyl-peptidase-4 -- Dcytb duodenal cytochrome b reductase -- FOXM1 Forkhead box M1 -- FOXM1-AS FOXM1 anti sens -- FPN ferroportin1 -- FTH ferritin -- FTH-1 ferritin heavy chain -- FTL ferritin light chain -- HO-1 heme oxygenase 1 -- HFE hemochromatosis protein -- HEPH hephaestin -- HIF hypoxia-inducible factor -- HP hepcidin -- Lcn2 lipocalin-2 -- LPCAT3 lysophosphatidylcholine acyltransferase 3 -- miRNA microRNA -- MZF1 myeloid zinc finger-1 -- NDRG1 N-myc downstream regulated gene-1 -- NOX-1 NADPH oxidase 1 -- Nramp2 natural resistance-associated macrophage protein 2 -- NRF2 nuclear factor erythroid 2-like2 -- PCFT proton-coupled folate transporter -- PUFAs polyunsaturated fatty acids -- TFR transferrin receptor -- Tf transferrin -- Tf-Fe2 holo-transferrin -- TFG-β1 transforming growth factor-beta1 -- WNT wingless; Cancer stem cells -- Iron metabolism -- Ferroptosis -- Cancer therapy -- Cell signaling -- Epigenetic; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2018.07.009
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Iron is an essential nutrient that facilitates cell proliferation and growth. Iron can be detrimental, however. The ability of iron to cycle between oxidized and reduced forms contributes to the formation of free radicals. An excess of free radicals leads to lipid peroxidation, more reactive oxygen species and oxidative stress, damage to DNA and other biomolecules, and, if potentially, tumorigenesis. Iron also has a role in the maintenance of the tumor 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 tumor cell survival. Recent studies have shed light on the role of iron metabolism in cancer stem cells (CSC) and suggest that specific targeting of iron metabolism in CSCs may improve the efficacy of cancer therapy. In this review, we first summarize briefly our current understanding of the intracellular processes involving iron, the effect of dietary iron, and its relation to cancer. We emphasize the importance of modifier "iron genes" in cancer and the possibility that these genes may encode biomarkers that may be used clinically. We then provide an update on the role of iron in metabolic reprogramming, the epithelial-mesenchymal transition, and the regulation of epigenetic marks essential for CSC maintenance and plasticity. Finally, we discuss the potential of targeting a recently discovered form of iron-regulated cell death, ferroptosis, in CSCs for treatment of cancer.