Iron as a Central Player and Promising Target in Cancer Progression

• Published in: International journal of molecular sciences Vol. 20; no. 2; p. 273
• Main Authors: Jung, Michaela, Mertens, Christina, Tomat, Elisa, Brüne, Bernhard
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.01.2019; MDPI
• Subjects: Anemia; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Biomarkers, Tumor - metabolism; Breast cancer; Cell division; Disease Progression; DNA Damage; Exports; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Homeostasis; Homology; Humans; Immune system; Inflammation; Iron; Iron - metabolism; iron chelators; iron homeostasis; Lipids; lipocalin-2; Liver; macrophage polarization; Medical prognosis; Mesenchyme; Metabolic Networks and Pathways - drug effects; Metabolism; Motility; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Oxidative Stress; Patients; Phenotypes; Proteins; Review; Spleen; Tumor cells; Tumor Microenvironment; Tumor necrosis factor-TNF; tumor progression; Tumors; iron chelators; macrophage polarization; tumor progression; iron homeostasis; lipocalin-2
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20020273

Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.