ArticleCell death & disease2023
Downregulation of EphA2 stability by RNF5 limits its tumor-suppressive function in HER2-negative breast cancers.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- RNF5 promotes acute lung injury through HSPA5 ER-to-cytosol translocation and resultant PERK activation.Cell death and differentiation · 2026Article
- The Interaction between the Tyrosine Kinase Receptor EphA2 and RNF5: Structural Insights from anComputational and structural biotechnology journal · 2026Article
- Dcaf15-mediated EphA2 degradation triggers disruption of the blood-brain barrier during Streptococcus suis meningitis.Communications biology · 2025Article
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- 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
- RING finger protein 5 protects against acute myocardial infarction by inhibiting ASK1.BMC cardiovascular disorders · 2024Article
- Hypoxia-induced TGFBI maintains glioma stem cells by stabilizing EphA2.Theranostics · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ephrin receptor A2 (EphA2) plays dual functions in tumorigenesis through ligand-independent tumor promotion or ligand-dependent tumor suppression. However, the regulation of EphA2 tumor-suppressive function remains unclear. Here, we showed that RNF5 interacts with EphA2 and induces its ubiquitination and degradation, decreases the stability and cell surface distribution of EphA2 and alters the balance of its phosphorylation at S897 and Y772. In turn, RNF5 inhibition decreases ERK phosphorylation and increases p53 expression through an increase in the EphA2 level in HER2-negative breast cancer cells. Consequently, RNF5 inhibition increases the adhesion and decreases the migration of HER2-negative breast cancer cells, and RNF5 silencing suppresses the growth of xenograft tumors derived from ER-positive, HER2-negative breast cancer cells with increased EphA2 expression and altered phosphorylation. RNF5 expression is inversely correlated with EphA2 expression in breast cancers, and a high EphA2 level accompanied by a low RNF5 level is related to better survival in patients with ER-positive, HER2-negative breast cancers. These studies revealed that RNF5 negatively regulates EphA2 properties and suppresses its tumor-suppressive function in HER2-negative breast cancers.
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