Division of Hematology-Oncology, The Hollings Cancer Center and Medical University of South Carolina, Charleston, SC, USA.
Onco Targets Ther. 2014 Sep 24;7:1663-87. doi: 10.2147/OTT.S37744. eCollection 2014.
The semaphorins, discovered over 20 years ago, are a large family of secreted or transmembrane and glycophosphatidylinositol -anchored proteins initially identified as axon guidance molecules crucial for the development of the nervous system. It has now been established that they also play important roles in organ development and function, especially involving the immune, respiratory, and cardiovascular systems, and in pathological disorders, including cancer. During tumor progression, semaphorins can have both pro- and anti-tumor functions, and this has created complexities in our understanding of these systems. Semaphorins may affect tumor growth and metastases by directly targeting tumor cells, as well as indirectly by interacting with and influencing cells from the micro-environment and vasculature. Mechanistically, semaphorins, through binding to their receptors, neuropilins and plexins, affect pathways involved in cell adhesion, migration, invasion, proliferation, and survival. Importantly, neuropilins also act as co-receptors for several growth factors and enhance their signaling activities, while class 3 semaphorins may interfere with this. In this review, we focus on the secreted class 3 semaphorins and their neuropilin co-receptors in cancer, including aspects of their signaling that may be clinically relevant.
信号素是 20 多年前发现的一个大家族，它们是最初被确定为轴突导向分子的分泌型或跨膜型和糖磷脂酰肌醇锚定蛋白，对神经系统的发育至关重要。现在已经确定，它们在器官发育和功能中也起着重要作用，特别是在免疫、呼吸和心血管系统中，并在包括癌症在内的病理紊乱中发挥作用。在肿瘤进展过程中，信号素可能具有促肿瘤和抗肿瘤功能，这使得我们对这些系统的理解变得复杂。信号素可能通过直接靶向肿瘤细胞，以及通过与微环境和脉管系统中的细胞相互作用和影响来影响肿瘤生长和转移。从机制上讲，信号素通过与其受体神经纤毛蛋白和丛蛋白结合，影响细胞黏附、迁移、侵袭、增殖和存活所涉及的途径。重要的是，神经纤毛蛋白也作为几种生长因子的共受体，并增强其信号活性，而 3 类信号素可能会干扰这种作用。在这篇综述中，我们重点介绍了癌症中的分泌型 3 类信号素及其神经纤毛蛋白共受体，包括其信号转导的某些方面可能具有临床相关性。
