Cell and Developmental Biology, Oregon Health & Science University, Portland, OR, USA.
Cancer Biol Ther. 2009 Sep;8(18):1699-708. doi: 10.4161/cbt.8.18.9146. Epub 2009 Sep 2.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Iron overload represents a significant risk factor in the development of HCC. Hereditary hemochromatosis (HH) is a genetic iron overload disease characterized by hepatic iron accumulation. The potential link between these two conditions leads to significant curiosity about regulation of iron homeostasis. Importantly, one of the HH genes, HAMP, encodes the master regulator of iron homeostasis, hepcidin, which is expressed by hepatocytes. Recent studies have shown that the remaining HH genes are either upstream regulators (HFE, HFE2 and TFR2) or downstream targets (FPN) of hepcidin. Moreover, the presence of additional signaling pathways in the liver that contribute to regulation of hepcidin expression has been documented. The function of these iron-regulatory proteins is currently being investigated to determine if they play a role in abnormal iron uptake in tumors. This review summarizes these recent studies and briefly discusses new directions in the treatment of iron overload in HCC patients.
肝细胞癌 (HCC) 是全球最常见的癌症之一。铁过载是 HCC 发展的一个重要危险因素。遗传性血色素沉着症 (HH) 是一种遗传性铁过载疾病，其特征是肝脏铁蓄积。这两种情况之间的潜在联系引起了人们对铁稳态调节的极大兴趣。重要的是，HH 基因之一 HAMP 编码铁稳态的主要调节剂——肝细胞表达的铁调素。最近的研究表明，HH 的其余基因要么是铁调素的上游调节剂（HFE、HFE2 和 TFR2），要么是下游靶点（FPN）。此外，肝脏中存在有助于铁调素表达调节的其他信号通路已被记录在案。目前正在研究这些铁调节蛋白的功能，以确定它们是否在肿瘤中异常铁摄取中发挥作用。本文综述了这些最新研究，并简要讨论了 HCC 患者铁过载治疗的新方向。
