Neufeld Gera, Shraga-Heled Niva, Lange Tali, Guttmann-Raviv Noga, Herzog Yael, Kessler Ofra
Cancer and Vascular Biology Research Center, Rappaport Research Institute in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
Front Biosci. 2005 Jan 1;10:751-60. doi: 10.2741/1569.
The semaphorins are the products of a large family of genes currently containing more than 30 members. These genes are divided into eight classes of which classes 1, 2 and 8 contain invertebrate and viral semaphorins, while classes 3-7 contain the vertebrate semaphorins. The semaphorins have been implicated in diverse developmental processes such as axon guidance during nervous system development and regulation of cell migration. Plexin receptors function as binding and signal transducing receptors for all semaphorins except for the class-3 semaphorins which bind to neuropilins which subsequently activate signaling through associated plexins. The class-3 semaphorins semaphorin-3B (s3b) and semaphorin-3F (s3f) function additionally as potent inhibitors of tumor development in small cell lung carcinoma. Recent evidence indicates that these semaphorins modulate the adhesive and migratory properties of responsive malignant cells. S3f as well as semaphorin-3A (s3a) were also found to function as inhibitors of angiogenesis, and it was shown that the anti-angiogenic properties of s3f contribute significantly to its anti-tumorigenic properties. In contrast with these inhibitory semaphorins, there is some evidence indicating that semaphorins such as semaphorin-3C (s3c), semaphorin-3E (s3e), semaphorin-4D (s4d), semaphorin-5C (s5c) semaphorin-6A (s6a) and semaphorin-6b (s6b) may contribute to tumorigenesis or to tumor progression. In this review we discuss the semaphorins, their receptors and their signal transduction mechanisms, and evidence linking semaphorins to the control of tumorigenesis and tumor progression.
信号素是一个目前包含30多个成员的大基因家族的产物。这些基因分为八类，其中第1、2和8类包含无脊椎动物和病毒信号素，而第3 - 7类包含脊椎动物信号素。信号素参与了多种发育过程，如神经系统发育过程中的轴突导向和细胞迁移的调控。除了与神经纤毛蛋白结合的3类信号素外，丛状蛋白受体作为所有信号素的结合和信号转导受体，神经纤毛蛋白随后通过相关的丛状蛋白激活信号传导。3类信号素中的信号素-3B（s3b）和信号素-3F（s3f）还额外发挥小细胞肺癌肿瘤发展强效抑制剂的作用。最近的证据表明，这些信号素调节反应性恶性细胞的黏附性和迁移特性。还发现S3f以及信号素-3A（s3a）具有血管生成抑制作用，并且表明s3f的抗血管生成特性对其抗肿瘤特性有显著贡献。与这些抑制性信号素相反，有一些证据表明，信号素-3C（s3c）、信号素-3E（s3e）、信号素-4D（s4d）、信号素-5C（s5c）、信号素-6A（s6a）和信号素-6B（s6b）等信号素可能促进肿瘤发生或肿瘤进展。在本综述中，我们讨论信号素、它们的受体及其信号转导机制，以及将信号素与肿瘤发生和肿瘤进展控制联系起来的证据。
