Role of semaphorins, neuropilins and plexins in cancer progression

Progress in understanding nervous system-cancer interconnections has emphasized the functional role of semaphorins (SEMAs) and their receptors, neuropilins (NRPs) and plexins (PLXNs), in cancer progression. SEMAs are a conserved and extensive family of broadly expressed soluble and membrane-associated proteins that were first described as regulators of axon guidance and neural and vascular development. However, recent advances have shown that they can have a dual role in cancer progression, acting either as tumor promoters or suppressors. SEMAs effects result from their interaction with specific co-receptors/receptors NRPs/PLXNs, that have also been described to play a role in cancer progression. They can influence both cancer cells and tumor microenvironment components modulating various aspects of tumorigenesis such as oncogenesis, tumor growth, invasion and metastatic spread or treatment resistance. In this review we focus on the role of these axon guidance signals and their receptors and co-receptors in various aspects of cancer. Furthermore, we also highlight their potential application as novel approaches for cancer treatment in the future.