Plexins are a family of nine single-pass transmembrane receptors with a conserved GTPase activating protein (GAP) domain. The plexin family is divided into four subfamilies: Type-A, type-B, type-C, and type-D plexins. Plexins function as receptors for axon guidance factors of the semaphorin family. The semaphorin gene family contains 22 genes that are divided into eight subclasses of which subclasses three to seven represent vertebrate semaphorins. The plexins and their semaphorin ligands have important roles as regulators of angiogenesis, cancer proliferation, and metastasis. Class 3 semaphorins, with the exception of sema3E, are the only semaphorins that do not bind directly to plexins. In order to transduce their signals, they bind instead to complexes consisting of receptors of the neuropilin family and various plexins. Some plexins also form complexes with tyrosine-kinase receptors such as the epidermal growth factor receptor ErbB2, the mesenchymal epithelial transition factor receptor (MET), and the Vascular endothelial growth factor receptor 2 (VEGFR2) and, as a result, can modulate cell proliferation and tumor progression. This review focuses on the roles of the different plexins in the control of cancer cell proliferation and invasiveness. Plexins also affect tumor progression and tumor metastasis by indirect mechanisms, such as modulation of angiogenesis and immune responses. However, these topics are not covered in the present review.
丛状蛋白是由九个单次跨膜受体组成的家族，具有保守的GTP酶激活蛋白结构域。该家族分为四个亚型：A型、B型、C型和D型丛状蛋白。它们作为信号素家族轴突导向因子的受体发挥作用。信号素基因家族包含22个基因，分为八个亚类，其中第三至第七亚类代表脊椎动物信号素。丛状蛋白及其信号素配体在血管生成、癌症增殖和转移调控中具有重要作用。除Sema3E外，第三类信号素是唯一不直接与丛状蛋白结合的亚型，其信号转导需通过与神经纤毛蛋白家族受体及不同丛状蛋白形成的复合物来实现。部分丛状蛋白还能与酪氨酸激酶受体形成复合物，如表皮生长因子受体ErbB2、间质上皮转化因子受体及血管内皮生长因子受体2，从而调控细胞增殖和肿瘤进展。本综述重点探讨不同丛状蛋白在控制癌细胞增殖和侵袭性中的作用。丛状蛋白还可通过调节血管生成和免疫反应等间接机制影响肿瘤进展和转移，但本文不作深入讨论。
Plexins as Regulators of Cancer Cell Proliferation, Migration, and Invasivity
肿瘤(癌症)患者之家