Disease relevance of EFNA1

• EPHA2/EFNA1 expression in human gastric cancer [1].
• A recent report, however, indicated that stimulation of the EPHA2 receptor ligand, ephrinA1 (EFNA1), inhibits the growth of EPHA2-expressing breast cancer [1].
• RESULTS: Normal bone specimens, osteosarcoma tissue specimens, and osteosarcoma cell lines expressed a distinct mRNA profile of ephrin-A1, ephrin-A4, and ephrin-B2 [2].
• Expression of ephrin-A1 was induced in melanoma cells by pro-inflammatory cytokines [3].
• Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells.CONCLUSION: EphA2 may serve as a novel target for bladder cancer therapy [4].

High impact information on EFNA1

• Although EphA/ephrin-A signaling organizes sensory maps within areas, and thalamocortical axons in the internal capsule, both papers argue that each developmental event is dissociable from the others [5].
• In prostatic epithelial cells and endothelial cells, but not fibroblasts, treatment with ephrin-A1 inhibits cell proliferation [6].
• Moreover, dominant-negative RhoA or inhibitor of Rho-associated kinase (Y27632) substantially negated the inhibitory effects of ephrin-A1 [7].
• Cotreatment with HGF and ephrin-A1 reduced sprouting of cell protrusions, an early step in branching morphogenesis [7].
• Capillary morphogenesis could be restored, however, by addition of recombinant ephrin A1/Fc fusion proteins [8].

Chemical compound and disease context of EFNA1

• In particular, dehydration stress led to slightly reduced levels of B61 RNA, and ABA application to young seedlings had no marked effect on its abundance [9].

Biological context of EFNA1

• Using Southern hybridization analysis of human x rodent somatic cell hybrid DNAs, we have assigned the genes that encode the GPI-anchored LERKs (EPLG1, EPLG3, and EPLG4) to human chromosome 1 [10].
• Ephrin-A1-induced chemotaxis and intracellular tyrosine phosphorylation, including EphA1 and Pyk2, was inhibited by Tyrphostin-A9 [11].
• Ephrin-A1 binding to CD4+ T cells stimulates both stromal cell-derived factor 1alpha (SDF-1alpha)- and macrophage inflammatory protein 3beta (MIP3beta)-mediated chemotaxis [11].
• Ephrin-A1 stimulation of Jurkat cells was also found to cause down-regulation of endogenous EphA3 receptors from the cell surface and their degradation [12].
• We show that ephrin-A1 stimulation of Jurkat T cells induces tyrosine phosphorylation of EphA3 receptors and cytoplasmic proteins, including the c-cbl proto-oncogene [12].

Anatomical context of EFNA1

• In contrast, EFNA1 was detected in all cell lines [1].
• Here we demonstrate that CD4+ T lymphocytes express the EphA1 and EphA4 receptors and that these cells bind the ligand ephrin-A1 [11].
• This, together with our finding that ephrin-A1 is expressed by HEV endothelial cells, suggests a role for Eph receptors in transendothelial migration [11].
• These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier [13].
• HT29 cells were transfected with EFNA1 antisense yielding clones that expressed less than 25% of EFNA1 found in vector controls [14].

Associations of EFNA1 with chemical compounds

• An ephrin-A-dependent signaling pathway controls integrin function and is linked to the tyrosine phosphorylation of a 120-kDa protein [15].
• Interactions between these molecules are promiscuous, but largely fall into two groups: EphA receptors bind to glycosylphosphatidyl inositol-anchored ephrin-A ligands, and EphB receptors bind to transmembrane ephrin-B proteins [16].
• Immunohistochemical examination showed that ephrin A1 was expressed on human endometrial luminal and glandular epithelial cells in both the proliferative (cycle d 8-13; n = 8) and secretory (cycle d 18-24; n = 7) phases [17].

Regulatory relationships of EFNA1

• Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2 [11].
• Ultimately, ephrin-A1 was found to inhibit chemokine-induced actin polymerization, thereby blocking migration [18].
• Ephrin-A1 stimulation prevented SDF-1alpha-induced activation of cdc42, while simultaneously inducing rho activation [18].
• Although TNF-alpha induces ephrin A1 expression in endothelial cells, the signaling pathways mediating ephrin A1 induction remain unknown [19].
• We showed that ephrin-A1 induced expression of AFP [20].

Other interactions of EFNA1

• Since the novel gene is the eighth member of the EPLG gene family, it is designated EPLG8 [21].
• Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for the HEK receptor [22].
• Importance of vascular phenotype by basic fibroblast growth factor, and influence of the angiogenic factors basic fibroblast growth factor/fibroblast growth factor receptor-1 and ephrin-A1/EphA2 on melanoma progression [23].
• Although strongly inhibiting chemotaxis, ephrin-A1 costimulus did not affect many of the signaling events downstream of the SDF-1alpha receptor CXCR4, including calcium flux and activation of MAPK [18].
• Soluble EphA2-Fc receptors inhibited ephrin-A1 ligand or VEGF-induced BRMEC migration and tube formation without affecting proliferation in vitro [24].

Analytical, diagnostic and therapeutic context of EFNA1

• The authors examined the expression of EPHA2 and EFNA1 using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in four gastric cancer cell lines and 49 primary gastric cancer samples, as well as in normal gastric tissue [1].
• Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system.RESULTS: Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines [4].
• In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry [4].
• Using cDNA microarray analysis, we previously found that ephrin-A1, an angiogenic factor, is the most differentially overexpressed gene in AFP producing hepatoma cell lines [20].
• Northern blot analysis also confirmed the expression of ephrin A1 mRNA in the endometrium [17].

References