The eph/ephrin system, an example of versatility and functional diversity in molecular biology of cancer and angiogenesis

Eph receptors and Ephrins are highly versatile regulators of processes as diverse as axon guidance, modulation of synaptic plasticity, morphogenesis of the vascular system or the patterning of organs. The Eph receptors are the largest family of receptor tyrosine kinases and their Ephrin ligands are bound to the plasmatic membrane or are transmembrane. The Eph/Ephrin system is characterized by activating bi-directional signals, throughout both the receptor and the ligand. By cell-cell contact, and depending on the expressed receptors set, cell type and context, it can trigger a wide array of cellular responses like cell adhesion, morphology, proliferation and migration. These roles are not confined to physiological processes, but are highly relevant for a variety of human pathologies and, in particular, cancer. EphrB4 receptor is overexpressed in various tumor types and with respect to its function, several published articles have shown discrepancies, since its activation can trigger pro-or anti-tumoral signals. The expression of its EphrinB2 ligand in both tumor cells and in the associated endothelium is related to its high vascularity. Thus, understanding the key mechanisms controlling Eph/Ephrin function would not only provide deeper insight into interesting biological principles, but it might also enable the development of new therapeutic reagents. For example, while antibodies against VEGF are already used for the treatment of cancer, inhibition of ephrin-B2 might be useful to simultaneously interfere with the function of VEGFR2 and VEGFR3, which act together during angiogenesis.