Netrin-1 and its receptors in tumour growth promotion

Abstract

Background: Netrin-1 belongs to a family of secreted proteins that act as migration and adhesion cues in the developing CNS and in a number of non-neural tissues. Netrin-1 is the ligand of deleted in colorectal cancer (DCC) and the uncoordinated family member 5 (UNC5) orthologues of the dependence receptor family. Over the past ten years, a novel mechanism has emerged, that a receptor unoccupied by its ligand is not necessarily inactive. Rather, such a receptor can mediate two signalling pathways, depending on whether it is bound to its ligand or not. In the absence of ligand, an active signalling pathway results in cell death through apoptosis. Objective: Coupled netrin-1 receptors have been shown to regulate diverse processes such as maintenance, integrity, migration and renewal of many tissues. We propose that netrin-1 receptors can regulate tumour development. Methods: We review the properties of netrin-1 and present netrin-1 receptors as regulators of tumourigenesis. Results/conclusion: Netrin-1 and its receptors are unexplored critical targets in cancer.

Keywords::

• apoptosis
• cancer
• DCC
• dependence receptor
• netrin-1
• UNC5

Acknowledgments

We would like to thank Patrick Mehlen for his suggestions and helpful comments, and Denis Ravel (Initial R&D Consulting) for his comments on therapy We apologise for not citing further interesting and important papers due to space limitations.