Divergent roles of Plexin D1 in cancer

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.