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

Figure 4

Summary of Potential Eph/Ephrin Tumor Promoting Pathways. A composite scheme of major tumorigenesis promoting Eph/ephrin signaling pathways is shown together. Ligand-independent forward signaling tumor promoting pathways shown for EphA and EphB receptors. Forward signaling pathways marked with an asterisk are known to be inhibited in ligand-dependent manner and participate in tumor suppression. Reverse signaling pathways are also shown for ephrin A and ephrin B. Yellow circles indicate phosphorylation of specific tyrosine/serine/threonine residues that are required for pathway activation. The broken bidirectional arrow represents cross-talk between Eph/ephrin and other types of receptors or pathways. Scissors symbol represents expression and/or function of proteases such as ADAM or MMP that are involved in the regulation of EphA and ephrin-B pathways, respectively. EMT indicates epithelial-to-mesenchymal transition. The figure is adapted from representative publications of Pasquale [8], Lisle et al. [9], Boyd et al. [10], and Xi et al. [11]. In addition, some of the pathways are substantiated from observations presented in several reports in the literature related to trastuzumab [12], COPII vesicles [13], NMDA receptor [14], E-cadherin [14], WNT pathway [15], and claudins [14, 16] for their relevance to tumor promoting pathways.