Regulation and misregulation of Eph/ephrin expression

The erythropoietin-producing hepatocellular (Eph) receptors form the largest family of receptor tyrosine kinases. Upon interaction of the Eph receptors with their ligands the ephrins, signaling cascades are initiated downstream of both receptor and ligand, a feature known as bidirectional signaling. The Eph receptors and ephrin ligands mediate important roles in embryonic development, particularly in establishing tissue organization by mediating cell adhesion or cell repulsion. In several adult tissues, at least one Eph/ephrin pair is found to play critical roles in tissue physiology and homeostasis. In recent years numerous members of this family have gained considerable attention since changes in their expression levels are a typical feature in cancer cells. Despite the fact that Eph/ephrin developmental expression profiles are well documented, little is known on transcriptional and post-transcriptional mechanisms that permits their highly specific, graded, complementary or overlapping expression patterns. Therefore understanding the transcriptional and post-transcriptional mechanisms regulating Eph/ephrin expression has far-reaching significance in biology. This review provides an overview of the mechanisms regulating Eph/ephrin expression. We highlight important emerging mechanisms of Eph/ephrin regulation or misregulation such as epigenetics and miRNAs.