Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers

Abstract

Eph receptors constitute the largest family of receptor tyrosine kinases, which are activated by ephrin ligands that either are anchored to the membrane or contain a transmembrane domain. These molecules play important roles in the development of multicellular organisms, and the physiological functions of these receptor-ligand pairs have been extensively documented in axon guidance, neuronal development, vascular patterning, and inflammation during tissue injury. The recognition that aberrant regulation and expression of these molecules lead to alterations in proliferative, migratory, and invasive potential of a variety of human cancers has made them potential targets for cancer therapeutics. We present here the involvement of Eph receptors and ephrin ligands in lung carcinoma, breast carcinoma, prostate carcinoma, colorectal carcinoma, glioblastoma, and medulloblastoma. The aberrations in their abundances are described in the context of multiple signaling pathways, and differential expression is suggested as the mechanism underlying tumorigenesis.

Tyrosine Kinase Receptors in Oncology

“…The following table details some of the TKR with their demonstrated functions [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ] ( Table 1 ).…”

Radiopharmacologist’s and Radiochemist’s View on Targeting the Eph/Ephrin Receptor Tyrosine Kinase System

“…On the other hand, Eph/ephrin signaling pathways have been characterized as pathophysiologically important in carcinogenesis and cancer progression as well as in neurological and inflammatory disorders. 1 − 3 Nevertheless, and in contrast to other RTKs that are already theranostically targeted to a greater extent, the development of Eph-/ephrin-directed drugs or tracers is still in its infancy.…”

“…A detailed description of Eph/ephrin expression in cancer was reviewed in detail elsewhere. 3 Eph/ephrin signaling is always context-dependent and strongly associated with a complex signaling network, which connects numerous pathways. The expression level of Eph/ephrins on cancer cells and the concomitants of different Eph receptors have different consequences.…”

“…The expression level of Eph/ephrins on cancer cells and the concomitants of different Eph receptors have different consequences. 3 Furthermore, one Eph receptor can mediate tumor-promoting effects with one ephrin ligand and opposite tumor-suppressing effects with another ephrin ligand. Eph/ephrin signaling in cancer functions via direct effects, e.g., on cell proliferation, cell survival, cellular motility, and invasiveness.…”

“…As in other B-type Eph/ephrins, reverse signaling from the EphB4-expressing cell to the ephrin-B2-expressing cell also plays an important role, e.g., by acting in a tumor-suppressive manner in some cancers, and is indispensable for regulation of tumor angiogenesis. 1 , 3 , 6 …”