Iron homeostasis in breast cancer.
Iron is an essential element and a critical component of molecules involved in energy production, cell cycle and intermediate metabolism. However, the same characteristic chemistry that makes it so biologically versatile may lead to iron-associated toxicity as a consequence of increased oxidative stress. The fact that free iron accumulates with age and generates ROS led to the hypothesis that it could be involved in the etiogenesis of several chronic diseases. Iron has been consistently linked to carcinogenesis, either through persistent failure in the redox balance or due to its critical role in cellular proliferation. Several reports have given evidence that alterations in the import, export and storage of cellular iron may contribute to breast cancer development, behavior and recurrence. In this review, we summarize the basic mechanisms of systemic and cellular iron regulation and highlight the findings that link their deregulation with breast cancer. To conclude, progresses in iron chelation therapy in breast cancer, as a tool to fight chemotherapy resistance, are also reviewed.
Unit for Multidisciplinary Biomedical Research (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Basic and Clinical Research on Iron Biology, Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal. Electronic address: oamarques@icbas.up.pt.
Oriana
O
Marques
Unit for Multidisciplinary Biomedical Research (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Berta Martins
BM
da Silva
Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Basic and Clinical Research on Iron Biology, Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal; Hematology Service, Santo António Hospital-Centro Hospitalar do Porto, Porto, Portugal.
Graça
G
Porto
Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Department of Pathology, Portuguese Oncology Institute (IPO), Porto, Portugal.
Carlos
C
Lopes
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000008:administration & dosage; D051381:Rats
D007502:Iron Chelating Agents; D007501:Iron
Breast cancer; Carcinogenesis; Iron chelation; Iron homeostasis