ArticleThe Journal of cell biology2013
EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion.
Article in The Journal of cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 93 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
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- Proteolytic EphA2 fragments cooperatively promote hepatocellular carcinoma progression.Cell death & disease · 2026Article
- Matrix Metalloproteinase 14 in Corneal Neovascularization.International journal of molecular sciences · 2026Review
- Frequent EPHA2 receptor mutations in cholangiocarcinoma disrupt receptor forward signaling supporting a tumor suppressor role.Biochimica et biophysica acta. Molecular cell research · 2026Article
- Proteomic Analysis of PTEN-Deficient Cells Reveals Src-Mediated Upregulation of EphA2 and Therapeutic Potential of Dual Inhibition.Molecular & cellular proteomics : MCP · 2025Article
- Polyploidy of MDA-MB-231 cells drives increased extravasation with enhanced cell-matrix adhesion.APL bioengineering · 2025Article
- Serum levels of EphA2 are elevated in knee osteoarthritis and associated with disease severity.Frontiers in medicine · 2025Article
- EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.World journal of gastrointestinal oncology · 2024Review
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 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
- EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma.Cancer research communications · 2023Article
- Opposite and dynamic regulation of the interferon response in metastatic and non-metastatic breast cancer.Cell communication and signaling : CCS · 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
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Changes in EphA2 signaling can affect cancer cell-cell communication and motility through effects on actomyosin contractility. However, the underlying cell-surface interactions and molecular mechanisms of how EphA2 mediates these effects have remained unclear. We demonstrate here that EphA2 and membrane-anchored membrane type-1 matrix metalloproteinase (MT1-MMP) were selectively up-regulated and coexpressed in invasive breast carcinoma cells, where, upon physical interaction in same cell-surface complexes, MT1-MMP cleaved EphA2 at its Fibronectin type-III domain 1. This cleavage, coupled with EphA2-dependent Src activation, triggered intracellular EphA2 translocation, as well as an increase in RhoA activity and cell junction disassembly, which suggests an overall repulsive effect between cells. Consistent with this, cleavage-prone EphA2-D359I mutant shifted breast carcinoma cell invasion from collective to rounded single-cell invasion within collagen and in vivo. Up-regulated MT1-MMP also codistributed with intracellular EphA2 in invasive cells within human breast carcinomas. These results reveal a new proteolytic regulatory mechanism of cell-cell signaling in cancer invasion.
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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.