Chédotal A, Kerjan G, Moreau-Fauvarque C
CNRS UMR7102, Equipe Développement Neuronal, Université Paris 6, Batiment B, Case 12, 9 Quai Saint-Bernard, 75005 Paris, France.
Cell Death Differ. 2005 Aug;12(8):1044-56. doi: 10.1038/sj.cdd.4401707.
Slits, semaphorins and netrins are three families of proteins that can attract or repel growing axons and migrating neurons in the developing nervous system of vertebrates and invertebrates. Recent studies have shown that they are widely expressed outside the nervous system and that they may play important roles in cancers. Several of the genes encoding these proteins are localized on chromosomal region associated with frequent loss-of-heterozygosity in tumors and cancer cell lines and there is also significant hypermethylation of their promoter suggesting that they may act as tumor suppressors. In addition, proteins in all these families and their receptors appear to control the vascularization of the tumors. Last, many axon guidance molecules also regulate cell migration and apoptosis in normal and tumorigenic tissues. Overall, this suggests that molecules that could mimick or block the activity of axon guidance molecules may be used as therapeutic agents for the treatment of malignancy.
缝隙蛋白、信号素和网蛋白是三类蛋白质家族，它们在脊椎动物和无脊椎动物发育中的神经系统中，能够吸引或排斥生长中的轴突以及迁移的神经元。最近的研究表明，它们在神经系统之外广泛表达，并且可能在癌症中发挥重要作用。编码这些蛋白质的几个基因定位于与肿瘤和癌细胞系中频繁杂合性缺失相关的染色体区域，并且它们的启动子也存在显著的高甲基化，这表明它们可能作为肿瘤抑制因子发挥作用。此外，所有这些家族中的蛋白质及其受体似乎都控制着肿瘤的血管生成。最后，许多轴突导向分子也调节正常组织和致瘤组织中的细胞迁移和凋亡。总体而言，这表明能够模拟或阻断轴突导向分子活性的分子可能用作治疗恶性肿瘤的治疗剂。
