Axon guidance cue Netrin-1 has dual function in angiogenesis

Angiogenesis is an important process required for cancer. Netrin-1, an axon guidance cue used to guide axon pathfinding and regulate neuron proliferation, may also be involved in the angiogenesis respecting the anatomical similarity of neural and vascular system. Surprisingly, we demonstrate that Netrin-1 has a dual role in regulating angiogenesis. It produces either facilitative or inhibitory effect depending upon its concentration. Moreover, UNC5B was the only subtype of Netrin-1 receptors detected in HUVECs in our study. Target knockdown of UNC5B in vascular endothelial cells, using a specific siRNA, resulted in a significant in cell proliferation and migration along with a loss of the inhibitory effect, regardless of concentration. Our study revealed Netrin-1 as a dual-function regulator of angiogenesis and its possible mechanism. The study might be used in anti-angiogenic therapies of cancer in the future.