文章：

铁和癌症：更多的矿石有待开采

Iron and cancer: more ore to be mined

原文发布日期：2013-04-18

DOI: 10.1038/nrc3495

类型: Review Article

开放获取: 否

要点：

1. Elemental iron is essential for cellular growth and homeostasis but it is potentially toxic to cells and tissues. Excess iron can contribute to tumour initiation and tumour growth.
2. Epidemiological evidence links increased body iron stores to increased cancer risk. High intake of dietary iron is associated with an increased risk for some cancers, particularly colorectal cancer. Hereditary haemochromatosis, a genetic disease that leads to excess iron accumulation, is associated with increased cancer risk.
3. Many types of cancer cells reprogramme iron metabolism in ways that result in net iron influx. They upregulate proteins that are involved in iron uptake, such as transferrin receptor 1 (TFR1), STEAP proteins and lipocalin 2 (LCN2), and decrease the expression of iron efflux proteins, such as ferroportin. Other iron-regulatory proteins, such as IRP1 and IRP2, contribute to cancer in ways that are less well understood.
4. Iron is crucial to many fundamental cellular processes, including DNA synthesis, proliferation, cell cycle regulation and the function of proteins containing iron–sulphur clusters. Iron–sulphur cluster-containing proteins include enzymes that contribute to maintaining genomic stability, as well as respiratory function.
5. Iron regulates crucial signalling pathways in tumours, including the hypoxia-inducible factor (HIF) and WNT pathways.
6. Measuring the expression of genes encoding proteins involved in iron metabolism may be useful in cancer prognosis. The expression of ferroportin, hepcidin, TFR1, haemochromatosis (HFE) and other genes involved in iron metabolism is linked to the prognosis of patients with breast cancer.
7. Iron is a target for cancer therapy. Iron chelators, TFR1 antibodies and cytotoxic ligands conjugated to transferrin (TF) represent some ways in which iron is being exploited therapeutically.

要点翻译：

1. 铁元素对细胞生长和稳态至关重要，但具有潜在细胞和组织毒性。过量铁会促进肿瘤发生与生长。
2. 流行病学证据表明体内铁储存增加与癌症风险升高相关。膳食铁的高摄入量与某些癌症（尤其是结直肠癌）风险增加存在关联。遗传性血色素沉着症作为一种导致铁过量蓄积的遗传性疾病，也与癌症风险增加相关。
3. 多种癌细胞通过重编程铁代谢实现铁净流入：上调转铁蛋白受体1、STEAP蛋白和脂质运载蛋白2等铁摄取相关蛋白，同时降低铁外排蛋白（如膜铁转运蛋白）的表达。其他铁调节蛋白如IRP1和IRP2在癌症中的作用机制尚未完全阐明。
4. 铁对DNA合成、增殖、细胞周期调控及含铁硫簇蛋白功能等基础细胞过程至关重要。含铁硫簇蛋白包括维持基因组稳定性的酶类以及呼吸功能相关酶。
5. 铁调控肿瘤中低氧诱导因子和WNT通路等关键信号通路。
6. 检测铁代谢相关蛋白编码基因的表达可能对癌症预后具有指导意义。膜铁转运蛋白、铁调素、转铁蛋白受体1、HFE血色素沉着症蛋白及其他铁代谢相关基因的表达与乳腺癌患者预后存在关联。
7. 铁已成为癌症治疗靶点：铁螯合剂、转铁蛋白受体1抗体以及与转铁蛋白偶联的细胞毒性配体等治疗策略正在被开发利用。

英文摘要：

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.

摘要翻译： 

铁是一种必需营养素，能促进细胞增殖与生长。然而，铁也具有参与氧化还原循环和自由基形成的能力。因此，铁既可促成肿瘤的发生，也可加速肿瘤生长；最新研究还表明，铁在肿瘤微环境及转移过程中发挥作用。铁的获取、外排、储存与调控通路在癌症中均发生紊乱，提示铁代谢重编程是肿瘤细胞存活的核心环节。缺氧诱导因子（HIF）和WNT信号通路可能共同导致癌症中铁代谢的改变。靶向铁代谢通路有望为癌症预后和治疗提供新手段。

原文链接：

Iron and cancer: more ore to be mined