Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine and Science, Jacksonville, FL, USA.
Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL, USA.
Biochim Biophys Acta Rev Cancer. 2019 Aug;1872(1):103-110. doi: 10.1016/j.bbcan.2019.05.004. Epub 2019 May 30.
Plexin D1 belongs to a family of transmembrane proteins called plexins. It was characterized as a receptor for semaphorins and is known to be essential for axonal guidance and vascular patterning. Mutations in Plexin D1 have been implicated in pathologic conditions such as truncus arteriosus and Möbius syndrome. Emerging data show that expression of Plexin D1 is deregulated in several cancers; it can support tumor development by aiding in tumor metastasis and EMT; and conversely, it can act as a dependence receptor and stimulate cell death in the absence of its canonical ligand, semaphorin 3E. The role of Plexin D1 in tumor development and progression is thereby garnering research interest for its potential as a biomarker and as a therapeutic target. In this review, we describe its discovery, structure, mutations, role(s) in cancer, and therapeutic potential.
Plexin D1 属于跨膜蛋白家族 plexins。它被表征为 semaphorin 的受体，并且对于轴突导向和血管形成至关重要。Plexin D1 的突变与诸如动脉干和 Möbius 综合征等病理状况有关。新出现的数据表明，Plexin D1 的表达在几种癌症中失调；它可以通过辅助肿瘤转移和 EMT 来支持肿瘤的发展；相反，它可以作为依赖受体，并且在没有其经典配体 semaphorin 3E 的情况下刺激细胞死亡。因此，Plexin D1 在肿瘤发生和进展中的作用因其作为生物标志物和治疗靶标的潜力而引起了研究兴趣。在这篇综述中，我们描述了它的发现、结构、突变、在癌症中的作用和治疗潜力。
