The Role of the Eph Receptor Family in Tumorigenesis

Abstract

The Eph receptor tyrosine kinase family, activated by binding to their cognate ephrin ligands, are important components of signalling pathways involved in animal development. More recently, they have received significant interest due to their involvement in oncogenesis. In most cases, their expression is altered, affecting the likes of cell proliferation and migration. Depending on the context, Eph receptors have the potential to act as both tumour promoters and suppressors in a number of cancers, such as breast cancer, colorectal cancer, lung cancer, prostate cancer, brain cancer and Kaposi’s sarcoma (KS), the latter being intrinsically linked to EphA2 as this is the receptor used for endothelial cell entry by the Kaposi’s sarcoma-associated herpesvirus (KSHV). In addition, EphA2 deregulation is associated with KS, indicating that it has a dual role in this case. Associations between EphA2 sequence variation and KSHV infection/KS progression have been detected, but further work is required to formally establish the links between EphA2 signalling and KS oncogenesis. This review consolidates the available literature of the role of the Eph receptor family, and particularly EphA2, in tumorigenesis, with the aim to develop a better understanding of Eph signalling pathways for potential targeting in novel cancer therapies.

Association Between Polymorphisms in Gastric Cancer Related Genes and Risk of Gastric Cancer: A Case-Control Study

“…The Eph family have been associated with controlling cell adhesion, migration and spatial organization of multicellular tissues (Anderton et al, 2021). There are at least 16 receptors and nine ligands recognized in various species belonging to the Eph family, which makes this family the largest family of receptor tyrosine kinases (Brantley-Sieders et al, 2006).…”

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

“…The Eph receptors are the largest family of RTKs, with 14 receptors divided into EphA and EphB subcategories, which bind to different types of ephrin ligands [ 329 ]. Eph/ephrin expression, clinical outcome and function in GB has been reviewed, including the use of Eph receptors as therapeutic targets [ 62 , 330 , 331 ]. A gradient of EphA receptor expression was observed in GB on the more de-differentiated stem-like cells and was absent on the less-aggressive differentiated tumor tissue [ 62 ].…”

Protein Co-expression Network-based Profiles Revealed from Laser-microdissected Cancerous Cells of Lung Squamous-Cell Carcinomas

“…Eph signaling regulates cell morphology and migration by modifying cell adhesion and organizing actin cytoskeleton and then affects cell proliferation and differentiation [36]. Eph receptors are expressed in cancer cells and the tumor microenvironment involved in tumorigenesis and metastasis [37]. However, Eph receptors can act both as tumor promoters and suppressors, depending on the cancer type [37,38].…”

“…Eph receptors are expressed in cancer cells and the tumor microenvironment involved in tumorigenesis and metastasis [37]. However, Eph receptors can act both as tumor promoters and suppressors, depending on the cancer type [37,38]. Regarding lung cancer, the upregulation or overexpression of EFNA1, EFNA2, EFNA4, EFNA5, and EFNA7 are indicative of tumor-promoting roles in lung cancer [39].…”