期刊
CANCERS
卷 11, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/cancers11081077
关键词
iron metabolism; cancer; mitochondrial iron; mitochondria; genetic theory of cancer; genetic instability; metabolism; labile iron pool; ferritin; transferrin receptors
类别
资金
- NIH [T32 CA078586, P01 CA217797, R01 CA169046, R01 CA182804]
- Gateway for Cancer Research [G-17-1500]
- Carver College of Medicine
- Holden Comprehensive Cancer center [NIH P30 CA086862]
Iron (Fe) is an essential element that plays a fundamental role in a wide range of cellular functions, including cellular proliferation, DNA synthesis, as well as DNA damage and repair. Because of these connections, iron has been strongly implicated in cancer development. Cancer cells frequently have changes in the expression of iron regulatory proteins. For example, cancer cells frequently upregulate transferrin (increasing uptake of iron) and down regulate ferroportin (decreasing efflux of intracellular iron). These changes increase the steady-state level of intracellular redox active iron, known as the labile iron pool (LIP). The LIP typically contains approximately 2% intracellular iron, which primarily exists as ferrous iron (Fe2+). The LIP can readily contribute to oxidative distress within the cell through Fe2+-dioxygen and Fenton chemistries, generating the highly reactive hydroxyl radical (HO center dot). Due to the reactive nature of the LIP, it can contribute to increased DNA damage. Mitochondrial dysfunction in cancer cells results in increased steady-state levels of hydrogen peroxide and superoxide along with other downstream reactive oxygen species. The increased presence of H2O2 and O-2(center dot-) can increase the LIP, contributing to increased mitochondrial uptake of iron as well as genetic instability. Thus, iron metabolism and labile iron pools may play a central role connecting the genetic mutational theories of cancer to the metabolic theories of cancer.
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