ArticleCell death & disease2022
Interactions between EGFR and EphA2 promote tumorigenesis through the action of Ephexin1.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- EphA2 as an oncogenic driver: roles and mechanisms of action in cancer.Molecular biology reports · 2026Review
- Exosomal EPHA2 transfers metastatic potential by stabilizing TGF-βRI and activating the TGF-β/SMAD3 signaling pathway in breast cancer.Cancer biology & medicine · 2026Article
- Regulation of receptor tyrosine kinase hetero-interactions.Current opinion in structural biology · 2025Review
- Up-regulation of NGEF via the BRAFBiochemistry and biophysics reports · 2025Article
- Article
- The role of Ephexin1 in translation and mTOR-targeted cancer therapy.Experimental & molecular medicine · 2025Article
- Neuronal guanine nucleotide exchange factor promotes the axonal growth and cancer cell proliferation via Ephrin-A3/EphA2 axis in lung adenocarcinoma.Journal of translational medicine · 2025Article
- Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation.Experimental & molecular medicine · 2025Article
- Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.Science advances · 2024Article
- 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
- NGEF is a potential prognostic biomarker and could serve as an indicator for immunotherapy and chemotherapy in lung adenocarcinoma.BMC pulmonary medicine · 2024Article
- Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Prognostic Markers in Tyrosine Kinases Specific to Basal-like 2 Subtype of Triple-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Ephexin3/ARHGEF5 Together with Cell Migration Signaling Partners within the Tumor Microenvironment Define Prognostic Transcriptional Signatures in Multiple Cancer Types.International journal of molecular sciences · 2023Article
- A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2-Bispecific Antibody for Combination Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Complexity of progranulin mechanisms of action in mesothelioma.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cell signaling factors EGFR, EphA2, and Ephexin1 are associated with lung and colorectal cancer and play an important role in tumorigenesis. Although the respective functional roles of EGFR and EphA2 are well known, interactions between these proteins and a functional role for the complex is not understood. Here, we showed that Ephexin1, EphA2, and EGFR are each expressed at higher levels in lung and colorectal cancer patient tissues, and binding of EGFR to EphA2 was associated with both increased tumor grade and metastatic cases in both cancer types. Treatment with Epidermal Growth Factor (EGF) induced binding of the RR domain of EGFR to the kinase domain of EphA2, and this binding was promoted by Ephexin1. Additionally, the AKT-mediated phosphorylation of EphA2 (at Ser897) promoted interactions with EGFR, pointing to the importance of this pathway. Two mutations in EGFR, L858R and T790M, that are frequently observed in lung cancer patients, promoted binding to EphA2, and this binding was dependent on Ephexin1. Our results indicate that the formation of a complex between EGFR, EphA2, and Ephexin1 plays an important role in lung and colorectal cancers, and that inhibition of this complex may be an effective target for cancer therapy.
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Registered trials
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