文章：

信号蛋白：肿瘤进展和肿瘤血管生成的多功能调节因子

The semaphorins: versatile regulators of tumour progression and tumour angiogenesis

原文发布日期：2008-06-26

DOI: 10.1038/nrc2404

类型: Review Article

开放获取: 否

要点：

1. Semaphorins are members of a large gene family of secreted and membrane-anchored proteins containing more than 20 vertebrate genes. They were initially characterized as axon guidance factors and are divided into eight subfamilies. The nine receptors belonging to the plexin family function as semaphorin receptors.
2. The secreted semaphorins belonging to the class 3 semaphorin subfamily are unique as they do not bind to plexins but instead bind to the neuropilin 1 or neuropilin 2 receptors. The neuropilins form complexes with members of the plexin family and function as the semaphorin binding elements and the plexins function as the signal transducing elements. The neuropilins also function as receptors for several pro-angiogenic factors, including several heparin-binding forms of vascular endothelial growth factor and hepatocyte growth factor.
3. Because of their role as transducers of pro-angiogenic signals, the neuropilins are viewed as targets for the development of anti-angiogenic drugs that function by inhibiting the binding of vascular endothelial growth factor to neuropilins.
4. The activation of plexins by semaphorins modulates cell adhesion and induces changes in the organization of the cytoskeleton of target cells. Prolonged exposure inhibits cell proliferation and induces apoptosis.
5. Several class 3 semaphorins such as semaphorin 3B and semaphorin 3F have been characterized as tumour suppressors.
6. The presence of neuropilins and plexins on endothelial cells also resulted in the realization that semaphorins such as semaphorin 3F and semaphorin 3A can function as anti-angiogenic factors and semaphorin 3F can inhibit the development of tumours by inhibition of tumour angiogenesis.
7. By contrast, semaphorins such as semaphorin 4D have been found to function as pro-angiogenic factors and to promote tumour progression.
8. Many types of tumour cells express semaphorin receptors. Several types of semaphorins have been found to induce pro-tumorigenic or anti-tumorigenic effects as a result of their interaction with semaphorin receptors expressed by tumour cells.

要点翻译：

1. 信号素是一个大型基因家族的成员，包括20多种脊椎动物基因编码的分泌型和膜锚定蛋白。它们最初被鉴定为轴突导向因子，可分为八个亚家族。属于丛蛋白家族的九种受体作为信号素受体发挥作用。
2. 属于3类信号素亚家族的分泌型信号素具有独特性，因为它们不与丛蛋白结合，而是与神经纤毛蛋白1或神经纤毛蛋白2受体结合。神经纤毛蛋白与丛蛋白家族成员形成复合物，作为信号素结合元件发挥作用，而丛蛋白则作为信号转导元件。神经纤毛蛋白还作为多种促血管生成因子的受体，包括多种肝素结合形式的血管内皮生长因子和肝细胞生长因子。
3. 由于神经纤毛蛋白在转导促血管生成信号中发挥作用，它们被视为开发抗血管生成药物的靶点，这类药物通过抑制血管内皮生长因子与神经纤毛蛋白的结合来发挥作用。
4. 信号素激活丛蛋白可调节细胞粘附并诱导靶细胞细胞骨架结构发生变化。长时间暴露会抑制细胞增殖并诱导细胞凋亡。
5. 几种3类信号素（如信号素3B和信号素3F）已被鉴定为肿瘤抑制因子。
6. 内皮细胞上神经纤毛蛋白和丛蛋白的存在也使人们认识到，信号素3F和信号素3A等信号素可作为抗血管生成因子发挥作用，且信号素3F可通过抑制肿瘤血管生成来抑制肿瘤发展。
7. 相比之下，信号素4D等信号素则被发现具有促血管生成作用并能促进肿瘤进展。
8. 多种类型的肿瘤细胞表达信号素受体。研究发现，若干信号素通过与肿瘤细胞表达的信号素受体相互作用，可诱导促肿瘤或抗肿瘤效应。

英文摘要：

The semaphorins and their receptors, the neuropilins and the plexins, were originally characterized as constituents of the complex regulatory system responsible for the guidance of axons during the development of the central nervous system. However, a growing body of evidence indicates that various semaphorins can either promote or inhibit tumour progression through the promotion or inhibition of processes such as tumour angiogenesis, tumour metastasis and tumour cell survival. This Review focuses on the emerging role of the semaphorins in cancer.

摘要翻译： 

信号蛋白及其受体——神经纤毛蛋白和丛蛋白——最初被描述为中枢神经系统发育过程中轴突导向的复杂调控系统的组成部分。然而，越来越多的证据表明，不同的信号蛋白可通过促进或抑制肿瘤血管生成、肿瘤转移及肿瘤细胞存活等过程，进而促进或抑制肿瘤进展。本综述聚焦于信号蛋白在癌症中的新兴作用。

原文链接：

The semaphorins: versatile regulators of tumour progression and tumour angiogenesis