ArticleCancer research2015
Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- Soluble N-terminal EphA2 fragment as a diagnostic biomarker and functional mediator of tumor progression in triple-negative breast cancer.Translational oncology · 2026Article
- Membrane-type I metalloproteinase (MT1-MMP): A key modifier of extracellular matrix microenvironment.The FEBS journal · 2026Review
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Proteolytic EphA2 fragments cooperatively promote hepatocellular carcinoma progression.Cell death & disease · 2026Article
- Matrix Metalloproteinase 14 in Corneal Neovascularization.International journal of molecular sciences · 2026Review
- Laminin-γ2-NR6A1 Fusion Protein Promotes Metastatic Potential in Non-Small-Cell Lung Carcinoma Cells without Epidermal Growth Factor Receptor Mutation.The American journal of pathology · 2025Article
- Development of an anti-human EphA2 monoclonal antibody EaBiochemistry and biophysics reports · 2025Article
- Serum EphA2 as a Promising Biomarker for the Early Detection and Diagnosis of Colorectal Cancer.Biomolecules · 2024Article
- EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Article
- Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review.Discover oncology · 2024Review
- A general approach for selection of epitope-directed binders to proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Downregulation of EphA2 stability by RNF5 limits its tumor-suppressive function in HER2-negative breast cancers.Cell death & disease · 2023Article
- EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma.Cancer research communications · 2023Article
- Proteolytic cleavage of membrane proteins by membrane type-1 MMP regulates cancer malignant progression.Cancer science · 2023Review
- Direct Identification of Proteolytic Cleavages on Living Cells Using a Glycan-Tethered Peptide Ligase.ACS central science · 2022Article
- Coordination of two kinesin superfamily motor proteins, KIF3A and KIF13A, is essential for pericellular matrix degradation by membrane-type 1 matrix metalloproteinase (MT1-MMP) in cancer cells.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Proteolytic modulation of tumor microenvironment signals during cancer progression.Frontiers in oncology · 2022Review
- Expression of Cancer Stem Cell Markers EpCAM and CD90 Is Correlated with Anti- and Pro-Oncogenic EphA2 Signaling in Hepatocellular Carcinoma.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Eph receptor tyrosine kinases are considered candidate therapeutic targets in cancer, but they can exert opposing effects on cell growth. In the presence of its ligands, Eph receptor EphA2 suppresses signaling by other growth factor receptors, including ErbB, whereas ligand-independent activation of EphA2 augments ErbB signaling. To deploy EphA2-targeting drugs effectively in tumors, the anti-oncogenic ligand-dependent activation state of EphA2 must be discriminated from its oncogenic ligand-independent state. Because the molecular basis for the latter is little understood, we investigated how the activation state of EphA2 can be switched in tumor tissue. We found that ligand-binding domain of EphA2 is cleaved frequently by the membrane metalloproteinase MT1-MMP, a powerful modulator of the pericellular environment in tumor cells. EphA2 immunostaining revealed a significant loss of the N-terminal portion of EphA2 in areas of tumor tissue that expressed MT1-MMP. Moreover, EphA2 phosphorylation patterns that signify ligand-independent activation were observed specifically in these areas of tumor tissue. Mechanistic experiments revealed that processing of EphA2 by MT1-MMP promoted ErbB signaling, anchorage-independent growth, and cell migration. Conversely, expression of a proteolysis-resistant mutant of EphA2 prevented tumorigenesis and metastasis of human tumor xenografts in mice. Overall, our results showed how the proteolytic state of EphA2 in tumors determines its effector function and influences its status as a candidate biomarker for targeted therapy.
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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.