ArticleThe Journal of biological chemistry2014
Transactivation of the receptor-tyrosine kinase ephrin receptor A2 is required for the low molecular weight hyaluronan-mediated angiogenesis that is implicated in tumor progression.
Article in The Journal of biological chemistry, 2014. 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, 37 citations in OpenAlex.
- Expression of CD44 and Its Spliced Variants: Innate and Inducible Roles in Nervous Tissue Cells and Their Environment.International journal of molecular sciences · 2025Review
- Intravenous Administration of Hyaluronan in Veterinary Musculoskeletal Disorders: Therapeutic Applications and Mechanisms.International journal of veterinary science and medicine · 2025Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Enhanced Tumor Accumulation of Low-Molecular-Weight Hyaluronic Acid/Chitosan Nanocomplexes for Photothermal Therapy.Pharmaceutics · 2023Article
- Hyaluronan and Its Receptors: Key Mediators of Immune Cell Entry and Trafficking in the Lymphatic System.Cells · 2021Review
- Research Progress on PATJ and Underlying Mechanisms Associated with Functional Outcomes After Stroke.Neuropsychiatric disease and treatment · 2021Review
- Article
- EphrinA1-Fc Attenuates Ventricular Remodeling and Dysfunction in Chronically Nonreperfused WT but not EphA2-R-M mice.International journal of molecular sciences · 2020Article
- Developing Body-Components-Based Theranostic Nanoparticles for Targeting Ovarian Cancer.Pharmaceutics · 2019Article
- Pancreatic cancer-initiating cell exosome message transfer into noncancer-initiating cells: the importance of CD44v6 in reprogramming.Journal of experimental & clinical cancer research : CR · 2019Article
- MicroRNA dysregulation in lung injury: the role of the miR-26a/EphA2 axis in regulation of endothelial permeability.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Elevated expression of hyaluronan synthase 2 associates with decreased survival in diffusely infiltrating astrocytomas.BMC cancer · 2018Article
- The blood-brain barrier internalises Cryptococcus neoformans via the EphA2-tyrosine kinase receptor.Cellular microbiology · 2018Article
- High and low molecular weight hyaluronic acid-coated gold nanobipyramids for photothermal therapy.RSC advances · 2018Article
- Article
- Overexpression and correlation of HIF-2α, VEGFA and EphA2 in residual hepatocellular carcinoma following high-intensity focused ultrasound treatment: Implications for tumor recurrence and progression.Experimental and therapeutic medicine · 2017Article
- Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Role of hyaluronan in pancreatic cancer biology and therapy: Once again in the spotlight.Cancer science · 2016Review
- Extracellular Vesicles from Caveolin-Enriched Microdomains Regulate Hyaluronan-Mediated Sustained Vascular Integrity.International journal of cell biology · 2015Article
- HABP2 is a Novel Regulator of Hyaluronan-Mediated Human Lung Cancer Progression.Frontiers in oncology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Angiogenesis or the formation of new blood vessels is important in the growth and metastatic potential of various cancers. Therefore, understanding the mechanism(s) by which angiogenesis occurs can have important therapeutic implications in numerous malignancies. We and others have demonstrated that low molecular weight hyaluronan (LMW-HA, ∼2500 Da) promotes endothelial cell (EC) barrier disruption and angiogenesis. However, the mechanism(s) by which this occurs is poorly defined. Our data indicate that treatment of human EC with LMW-HA induced CD44v10 association with the receptor-tyrosine kinase, EphA2, transactivation (tyrosine phosphorylation) of EphA2, and recruitment of the PDZ domain scaffolding protein, PATJ, to the cell periphery. Silencing (siRNA) CD44, EphA2, PATJ, or Dbs (RhoGEF) expression blocked LMW-HA-mediated angiogenesis (EC proliferation, migration, and tubule formation). In addition, silencing EphA2, PATJ, Src, or Dbs expression blocked LMW-HA-mediated RhoA activation. To translate our in vitro findings, we utilized a novel anginex/liposomal targeting of murine angiogenic endothelium with either CD44 or EphA2 siRNA and observed inhibition of LMW-HA-induced angiogenesis in implanted Matrigel plugs. Taken together, these results indicate LMW-HA-mediated transactivation of EphA2 is required for PATJ and Dbs membrane recruitment and subsequent RhoA activation required for angiogenesis. These results suggest that targeting downstream effectors of LMW-HA could be a useful therapeutic intervention for angiogenesis-associated diseases including tumor progression.
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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.