ArticleThe Journal of clinical investigation2008
The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
175 citing papers in PubMed, 1 synthesis or guideline pooled it, 276 citations in OpenAlex.
- The Value of EphB2 Receptor and Cognate Ephrin Ligands in Prognostic and Predictive Assessments of Human Breast Cancer.International journal of molecular sciences · 2021Pooled it
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Protein-protein interactions as therapeutic targets in breast cancer: integrated computational and experimental advances, mechanisms and clinical translation.Molecular biology reports · 2026Review
- EPHA3, upregulated in high-risk histological subtypes of gastrointestinal stromal tumor, promotes GIST progression.Radiology and oncology · 2026Article
- Inhibition of EphA2 triggers ferroptosis by disrupting USP38mediated SLC7A11 stabilization in chemoresistant gastric cancer.Cellular and molecular life sciences : CMLS · 2026Article
- EphA2 as an oncogenic driver: roles and mechanisms of action in cancer.Molecular biology reports · 2026Review
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
- Manifold roles of the chemokine G-protein-coupled receptor CCR7 in differentiation of human trophoblast into extravillous and syncytiotrophoblast lineages.Development (Cambridge, England) · 2025Article
- Article
- Eph Receptors Activate Myeloid Checkpoint Receptor LILRB5 to Support Tumor Development.Cancer immunology research · 2025Article
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- Exploring the complex role of the Eph/Ephrin signaling in oral and maxillofacial cancers.Frontiers in oncology · 2025Review
- Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.Science advances · 2024Article
- Article
- Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review.Discover oncology · 2024Review
- Targeting the EphA2 pathway: could it be the way for bone sarcomas?Cell communication and signaling : CCS · 2024Review
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity.Cell communication and signaling : CCS · 2024Review
- Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Targeting Interleukin-13 Receptor α2 and EphA2 in Aggressive Breast Cancer Subtypes with Special References to Chimeric Antigen Receptor T-Cell Therapy.International journal of molecular sciences · 2024Review
115 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Overexpression of the receptor tyrosine kinase EPH receptor A2 (EphA2) is commonly observed in aggressive breast cancer and correlates with a poor prognosis. However, while EphA2 has been reported to enhance tumorigenesis, proliferation, and MAPK activation in several model systems, other studies suggest that EphA2 activation diminishes these processes and inhibits the activity of MAPK upon ligand stimulation. In this study, we eliminated EphA2 expression in 2 transgenic mouse models of mammary carcinoma. EphA2 deficiency impaired tumor initiation and metastatic progression in mice overexpressing ErbB2 (also known as Neu) in the mammary epithelium (MMTV-Neu mice), but not in mice overexpressing the polyomavirus middle T antigen in mammary epithelium (MMTV-PyV-mT mice). Histologic and ex vivo analyses of MMTV-Neu mouse mammary epithelium indicated that EphA2 enhanced tumor proliferation and motility. Biochemical analyses revealed that EphA2 formed a complex with ErbB2 in human and murine breast carcinoma cells, resulting in enhanced activation of Ras-MAPK signaling and RhoA GTPase. Additionally, MMTV-Neu, but not MMTV-PyV-mT, tumors were sensitive to therapeutic inhibition of EphA2. These data suggest that EphA2 cooperates with ErbB2 to promote tumor progression in mice and may provide a novel therapeutic target for ErbB2-dependent tumors in humans. Moreover, EphA2 function in tumor progression appeared to depend on oncogene context, an important consideration for the application of therapies targeting EphA2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.