| 2002 |
EFNA1 (ephrinA1) is a GPI-anchored ligand that preferentially binds to the receptor tyrosine kinase EphA2; activation of EphA2 by EFNA1 in HT29 colon carcinoma cells leads to tyrosine hyperphosphorylation of EphA2, E-cadherin, and beta-catenin, and reduced EFNA1 expression slows three-dimensional spheroid growth but not monolayer growth, implicating autocrine EFNA1-EphA2 signaling in overcoming contact inhibition. |
Antisense transfection to reduce EFNA1 expression, EFNA1-Fc stimulation, western blot for phosphorylation of EphA2/E-cadherin/beta-catenin, 3D spheroid vs monolayer growth assay |
Cancer letters |
Medium |
11741747
|
| 2005 |
Stimulation of EPHA2-expressing gastric cancer cell lines with soluble ephrinA1-Fc (EFNA1) leads to decreased EphA2 protein expression, increased EphA2 phosphorylation, and inhibition of cell growth upon repetitive stimulation, demonstrating that EFNA1 engagement of EphA2 triggers receptor downregulation and growth suppression. |
Stimulation with soluble ephrinA1-Fc, western blotting, northern blotting, RT-PCR, cell growth assay |
Cancer science |
Medium |
15649254
|
| 2006 |
Efna1 (ephrinA1) is expressed in overlapping and complementary domains with its receptor Epha1 and paralog Efna3 in the primitive streak and posterior paraxial mesoderm during early mouse development, consistent with bidirectional Eph-ephrin signaling regulating cell migratory and adhesive behavior in this context. |
Whole-mount in situ hybridization in early mouse embryos |
Gene expression patterns : GEP |
Low |
16466970
|
| 2018 |
The lncRNA GMAN promotes translation of EFNA1 mRNA into protein by competitively binding GMAN-AS (an antisense RNA complementary to EFNA1 mRNA), thereby preventing GMAN-AS from suppressing EFNA1 translation; elevated EFNA1 protein in turn promotes gastric cancer cell invasion and metastasis, as demonstrated by rescue of GMAN-knockdown invasive phenotype by ectopic EFNA1 expression. |
RNA pulldown and mapping assays, polysome profiling, siRNA/shRNA knockdown, CRISPR/Cas9 knockout, overexpression, Transwell invasion assay, mouse xenograft metastasis model, immunoblot |
Gastroenterology |
High |
30445010
|
| 2012 |
A SNP (rs12904, G>A) in the 3'UTR of EFNA1 alters the binding site for hsa-miR-200c; luciferase assays confirmed EFNA1 as a direct target of miR-200c and showed that the G allele reduces miR-200c-mediated suppression of EFNA1 expression, while the A allele permits stronger miR-200c-mediated repression. |
Luciferase reporter assay, case-control genotyping, qRT-PCR on patient tumor tissues |
Molecular carcinogenesis |
Medium |
23065816
|
| 2025 |
EFNA1 cis-interacts with its receptor EphA2 on the same cell surface in cervical cancer cells, leading to decreased EphA2 tyrosine phosphorylation and subsequent activation of the Src/AKT/STAT3 forward signaling pathway; inhibition of this pathway with specific inhibitors attenuated tumorigenic capacity, and EFNA1 expression is driven by a tumor-specific super-enhancer containing FOSL2 binding sites whose knockdown suppresses both H3K27ac enrichment and luciferase activity at the SE region. |
Integrated epigenomic/transcriptomic profiling, FOSL2 knockdown with luciferase and ChIP assays, EFNA1 knockdown, specific pathway inhibitors, in vitro and in vivo tumor models |
The Journal of clinical investigation |
Medium |
39964764
|
| 2025 |
Flagellin-induced TLR5 signaling causes ADAM9 metalloproteinase-dependent cleavage/shedding of EFNA1 from airway epithelial cells, disrupting EPHA2-EFNA1 trans-binding and activating ligand-independent EPHA2 signaling; EPHA2 ablation reduced inflammatory responses to flagellin and Pseudomonas aeruginosa, and forced EFNA1 shedding alone (without PAMPs) was sufficient to stimulate inflammatory responses, establishing EFNA1 shedding as a pathogen-sensing mechanism. |
EFNA1 cleavage assay, ADAM9 inhibition/knockdown, EPHA2 knockout, in vitro and in vivo (mouse) flagellin/P. aeruginosa challenge, inflammatory cytokine readout |
iScience |
High |
39991543
|
| 2025 |
In HNSCC cells, EFNA1 knockdown reduces activity of the AKT/ERK1/2 signaling pathway, and EFNA1 overexpression increases cell proliferation that is reversible by EFNA1 antibody treatment, establishing that EFNA1 promotes survival signaling through AKT/ERK1/2. |
EFNA1 knockdown and overexpression, western blotting for EphA2pS898/EphA2/EFNA1/AKT/ERK1/2, cell proliferation and apoptosis assays |
Biochemical and biophysical research communications |
Medium |
40578286
|
| 2025 |
In diabetic retinopathy, IL-15 secreted by monocytes/macrophages activates STAT5 in endothelial cells, which binds the EFNA1 promoter in an NCOA2-dependent manner to induce EFNA1 expression and promote angiogenesis; EFNA1 and NCOA2 form a positive feedback loop where knockdown of either gene reduces expression of the other. |
STAT5 inhibition, NCOA2 knockdown, EFNA1 knockdown, ChIP-implied STAT5 promoter binding assay, co-culture with THP-1 under high-glucose conditions, angiogenesis assays |
Molecular vision |
Medium |
41867368
|
| 2026 |
Diclofenac reduces EFNA1 expression in breast cancer cells by impairing EPAS1 (HIF-2α) binding to the EFNA1 promoter region (-1353 to -782); EFNA1 overexpression rescues the anti-tumor effects of diclofenac, establishing EFNA1 as the critical mediator of diclofenac's COX-independent anti-cancer activity. |
RNA-seq, luciferase reporter assay for EFNA1 promoter, EFNA1 overexpression rescue, qRT-PCR, western blot, xenograft model |
Current medicinal chemistry |
Medium |
41941163
|
| 2025 |
In esophageal squamous cell carcinoma, EFNA1 knockdown suppresses cMYC expression and its downstream cell cycle genes and activates autophagy; similar effects are seen with knockdown of its receptor EPHA2, placing EFNA1 upstream of the EPHA2-cMYC-cell cycle/autophagy axis. |
EFNA1 and EPHA2 knockdown, CCK-8 and colony formation assays, wound healing, flow cytometry (cell cycle), transmission electron microscopy (autophagolysosome), western blot |
Discover oncology |
Medium |
37160815
|
| 1996 |
EFNA1 (LERK-1/EPLG1) encodes a GPI-anchored membrane protein belonging to the LERK family of Eph receptor ligands and is located on human chromosome 1q21-q22; its GPI anchor distinguishes it from transmembrane LERKs and is consistent with bidirectional signaling via Eph receptors. |
Southern hybridization of somatic cell hybrid DNAs, fluorescence in situ hybridization, interspecific backcross mapping |
Genomics |
Medium |
8660976
|