Roles of EphA2 in Development and Disease

Abstract

The Eph family of receptor tyrosine kinases (RTKs) has been implicated in the regulation of many aspects of mammalian development. Recent analyses have revealed that the EphA2 receptor is a key modulator for a wide variety of cellular functions. This review focuses on the roles of EphA2 in both development and disease.

Overexpressed oncogenic tumor-self antigens

“…39 This family and its ligands play key roles in normal development and in tumorigenesis, where EphA2 is overexpressed in multiple cancers including brain malignancies, which have been the focus of most vaccine trials. 40 The vaccine potential of targeting EphA2 in gliomas was initially demonstrated by generating HLA-A2-restricted CTLs from the peripheral blood of HLA-A2C normal donors and glioma patients using a single synthetic peptide (TLADFDPRV), and by vaccination of HHD mice with the same EphA2 peptide, demonstrating that tolerance could be broken by vaccination without inducing autoimmunity.…”

Emerging and Diverse Functions of the EphA2 Noncanonical Pathway in Cancer Progression

“…[1][2][3][4][5][6][9][10][11][12][13][14][15][17][18][19]35) Normally, EphA2 binds to ephrin-A1 on its neighboring cells and influences cell proliferation, survival, migration, morphology, cell-cell repulsion and adhesion in embryonic development, axon guidance, synaptogenesis, angiogenesis, and casculogenesis (Fig. 1).…”

“…[1][2][3][4][5][6][9][10][11][12][13][14][15][17][18][19] Forward signaling induces Eph receptor oligomer clustering, cross-phosphorylation of each other's tyrosine residues on the juxtamembrane domain and activation loop, and, consequently, evokes kinase activity. Some proteins, including a Ras family guanosine triphosphatase (GTPase)-activating protein, guanine-nucleotide exchange factors, Vav, ephexin, focal adhesion kinase (FAK), Src family cytoplasmic tyrosine kinases, and the p85 subunit of phosphatidylinositol 3-kinase (PI3K), have been reported to interact with activated receptors and regulate the signaling.…”

“…7,8) While it is expressed in normal epidermal cells, including the skin, kidney, liver, lung, small intestine, colon, and lens, the expression of EphA2 is inhibited in these differentiated tissues. 9,10) On the other hand, various solid tumors, such as breast, ovary, prostate, pancreas, glioblastoma, neck, renal, lung, melanoma, bladder, gastric esophageal, colorectal, and cervical cancers, were reported to express high levels of EphA2. [11][12][13][14][15][16][17] Of note, its expression is associated with a more aggressive cancer phenotype and correlated with tumor metastasis and poor patient survival.…”

Inherited Congenital Cataract: A Guide to Suspect the Genetic Etiology in the Cataract Genesis

“…Apparently, the downstream signaling of activated EPHA2 promotes the antioxidative capacity of lens epithelial cells to eradicate the overproduction of reactive oxygen species . It is probable that the loss of EPHA2 function could affect the structural stability of the cell, cell-to-cell crosstalk, protein folding and transcriptional activation [Park et al, 2013]. Thus, the cytoprotective and antiapoptotic functions of EPHA2 in the lens indicate the possible role of EPHA2 in avoiding lens opacity.…”