文章：

裂隙和网络的新作用：轴突引导线索作为抗癌靶点？

Novel roles for Slits and netrins: axon guidance cues as anticancer targets?

原文发布日期：2011-02-17

DOI: 10.1038/nrc3005

类型: Review Article

开放获取: 否

要点：

1. The axon guidance cues netrin 1 and Slits are causally implicated in human cancer. They are deregulated in a large proportion of human cancer, and the analysis of various mouse models has revealed that this deregulation is associated with tumour progression.
2. Netrin 1, Slits and their respective receptors are implicated in tumorigenesis via the regulation of tumour cell migration, tumour cell survival and tumour angiogenesis.
3. The netrin 1 receptors deleted in colorectal cancer (DCC) and UNC5 (UNC5A, UNC5B, UNC5C and UNC5D) are dependence receptors. They actively trigger apoptosis in the absence of netrin 1. This activity can function as a safeguard mechanism against tumour development.
4. Slits–roundabout receptors (Robos) have a dual role in regulating angiogenesis. SLIT2–ROBO1 inhibits angiogenesis while SLIT2–ROBO4 promotes the stability of established vessels.
5. Netrin 1 is upregulated in a large proportion of cancers, and an appealing therapeutic strategy could be to inhibit the interaction of netrin 1 with its receptors.

要点翻译：

1. 轴突导向因子netrin 1与Slits家族蛋白被证实与人类癌症存在因果关联。这些因子在大部分人类癌症中呈现异常调控，通过对多种小鼠模型的分析发现，这种异常调控与肿瘤进展密切相关。
2. Netrin 1、Slits及其相应受体通过调控肿瘤细胞迁移、肿瘤细胞存活和肿瘤血管生成参与肿瘤发生过程。
3. 结直肠癌缺失基因（DCC）和UNC5受体家族（UNC5A、UNC5B、UNC5C和UNC5D）作为netrin 1的依赖性受体，在netrin 1缺失时会主动触发细胞凋亡。这种活性可发挥抑制肿瘤发展的保护机制。
4. Slits–Roundabout（Robo）受体在调控血管生成中具有双重作用：SLIT2–ROBO1能抑制血管生成，而SLIT2–ROBO4则促进已形成血管的稳定性。
5. Netrin 1在大部分癌症中表达上调，因此抑制netrin 1与其受体的相互作用可能成为极具前景的治疗策略。

英文摘要：

Over the past few years, several genes, proteins and signalling pathways that are required for embryogenesis have been shown to regulate tumour development and progression by playing a major part in overriding antitumour safeguard mechanisms. These include axon guidance cues, such as Netrins and Slits. Netrin 1 and members of the Slit family are secreted extracellular matrix proteins that bind to deleted in colorectal cancer (DCC) and UNC5 receptors, and roundabout receptors (Robos), respectively. Their expression is deregulated in a large proportion of human cancers, suggesting that they could be tumour suppressor genes or oncogenes. Moreover, recent data suggest that these ligand–receptor pairs could be promising targets for personalized anticancer therapies.

摘要翻译： 

过去几年中，一些对胚胎发育至关重要的基因、蛋白和信号通路被证实通过主导抗肿瘤保护机制的失效，在调控肿瘤的发生和进展中发挥关键作用。其中包括轴突导向因子，如Netrin和Slit家族。Netrin-1及Slit家族成员是分泌型细胞外基质蛋白，分别结合结直肠癌缺失蛋白（DCC）/UNC5受体及 roundabout受体（Robos）。这些分子在多种人类癌症中表达失调，提示其可能作为抑癌基因或癌基因发挥作用。此外，最新研究表明，这些配体-受体对有望成为个体化抗癌治疗的潜力靶点。

原文链接：

Novel roles for Slits and netrins: axon guidance cues as anticancer targets?