Background information
The UNC5H family of proteins act as transmembrane receptors for netrin-1 and play a crucial role in axon guidance and migration of neural cells. Additionally, UNC5H receptors induce apoptosis when cleaved by a caspase, producing an intracellular fragment containing a death domain. This activity is blocked by the binding of netrin-1. In the absence of netrin-1, UNC5H receptors act as tumor suppressors by inhibiting anchorage-independent growth and invasion, but mutation of these receptors provides a potential mechanism for tumorigenicity. The expression of UNC5H receptors is down-regulated in multiple cancers, including colorectal, breast, ovary, uterus, stomach, lung, and kidney cancers. UNC5H3, also known as UNC5C, plays an important role in the development of spinal accessory motor neurons. It is also involved in mediating the repulsive action for netrin-1 and it serves as a stop signal for migratory cells.
