A review on Eph/ephrin, angiogenesis and lymphangiogenesis in gastric, colorectal and pancreatic cancers

Abstract

Erythroprotein-producing human hepatocellular carcinoma receptors (Eph receptors) compose a subfamily of transmembrane protein-tyrosine kinases receptors that takes part in numerous physiological and pathological processes. Eph family receptor-interacting proteins (Ephrins) are ligands for those receptors. Eph/ephrin system is responsible for the cytoskeleton activity, cell adhesion, intercellular connection, cellular shape as well as cell motility. It affects neuron development and functioning, bone and glucose homeostasis, immune system and correct function of enterocytes. Moreover Eph/ephrin system is one of the crucial ones in angiogenesis and lymphangiogenesis. With such a wide range of impact it is clear that disturbed function of this system leads to pathology. Eph/ephrin system is involved in carcinogenesis and cancer progression. Although the idea of participation of ephrin in carcinogenesis is obvious, the exact way remains unclear because of complex bi-directional signaling and cross-talks with other pathways. Further studies are necessary to find a new target for treatment.

Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases

“…Filtering for only differentially expressed genes, we found a total of 63 putative signaling interactions ( Figure 5c ). Notably, 19 of these interactions were between SPARC + COL3A1 + fibroblasts and endothelial cells, including Notch activation through the DLL4:NOTCH3 interaction, as described earlier in the synovium (Wei et al, 2020), as well as morphogen TGF β , growth factor PDGF β , angiogenic factors Ephrin- α and Ephrin- β (Rudno-Rudzińska et al, 2017), and angiogenic and mitogenic factors MDK and PTN (Weckbach et al, 2012). This large variety of putative signaling interactions ( Figure 5c ), both from and to endothelial cells, suggests that SPARC+COL3A1+ fibroblasts participate in signaling crosstalk with endothelial cells.…”

Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics

“…In contrast, increased lymphangiogenesis enables cancer metastasis similar to that of angiogenesis, where tumor cells are able to invade and travel through the vasculature (31). Interestingly, a major transcription factor of LECs, Prox1, was found to be overexpressed in multiple cancers, promoting not only lymphangiogenesis but also cancer cell migration capacity as well as invasiveness (32)(33)(34).…”

EPHA2 Is a Predictive Biomarker of Resistance and a Potential Therapeutic Target for Improving Antiepidermal Growth Factor Receptor Therapy in Colorectal Cancer

“…[7][8][9]. In a variety of malignancies, different ephrins and/or its receptors, including EPHA2, are activated, potentially contributing to increased malignancy and poor prognosis (7)(8)10). In colorectal cancer, EPHA2 and ephrin A1 were found significantly overexpressed in stages I to II compared with stages III to IV, suggesting a potential role in the early stages of disease development (11).…”