Points of therapeutic intervention along the Wnt signaling pathway in hepatocellular carcinoma.
Points of therapeutic intervention along the Wnt signaling pathway in hepatocellular carcinoma.
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DOI：
10.2174/187152011796011019
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发表时间：
2011-06
影响因子：
2.8
通讯作者：
Sarah B. Nambotin;J. Wands;Miran Kim
中科院分区：
文献类型：
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作者：
Sarah B. Nambotin;J. Wands;Miran Kim
肝细胞癌（HCC）是全球癌症死亡的第三大原因。然而，对于这种破坏性肿瘤的靶向治疗方法知之甚少。肝癌中生长因子信号通路失调控，有证据表明WNT/ frizzled介导的信号通路在肝癌发生中起关键作用。HCC中信号的异常激活主要是由于Wnt/β-catenin信号成分的表达失调。这导致β-catenin/TCF依赖靶基因的激活，这些基因控制细胞增殖、细胞周期、凋亡或运动。研究表明，Wnt/β-catenin信号级联的破坏在HCC中显示出抗癌特性。目前，还没有针对WNT通路的治疗分子可用或处于临床评估中用于治疗HCC。本文将讨论已确定的与典型WNT信号通路相关的潜在分子靶点及其潜在的治疗作用。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. However, there is little known about targeted therapeutics for the treatment of this devastating tumor. Among the growth factor signaling cascades deregulated in HCC, evidences suggest that the WNT/Frizzled-mediated signaling pathway plays a key role in the hepatic carcinogenesis. Aberrant activation of the signaling in HCC is mostly due to deregulated expression of the Wnt/β-catenin signaling components. This leads to the activation of the β-catenin/TCF dependent target genes, which controls cell proliferation, cell cycle, apoptosis or motility. It has been shown that disruption of the Wnt/β-catenin signaling cascade displayed anti-cancer properties in HCC. Currently, no therapeutic molecules targeting the WNT pathway are available or under clinical evaluation for the treatment of HCC. This review will discuss the identified potential molecular targets related to the canonical WNT signaling pathway and their potential therapeutic usefulness.