ArticleCellular signalling2011
Crosstalk of the EphA2 receptor with a serine/threonine phosphatase suppresses the Akt-mTORC1 pathway in cancer cells.
Article in Cellular signalling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 105 citations in OpenAlex.
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Exploring Mitochondrial Autophagy Dysregulation in Osteosarcoma: Its Implications for Prognosis and Targeted Therapy.Combinatorial chemistry & high throughput screening · 2026Article
- EphA2 regulates vascular permeability and prostate cancer metastasis via modulation of cell junction protein phosphorylation.Oncogene · 2025Article
- Article
- Probing phosphorylation events in biological membranes: The transducer function.Biochimica et biophysica acta. Biomembranes · 2024Review
- Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review.Discover oncology · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Time-resolved live-cell spectroscopy reveals EphA2 multimeric assembly.Science (New York, N.Y.) · 2023Article
- A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Review
- A computational and laboratory approach for the investigation of interactions of peptide conjugated natural terpenes with EpHA2 receptor.Journal of molecular modeling · 2023Article
- Eph Receptors in Cancer.Biomedicines · 2023Review
- Loss of H3K27 Trimethylation Promotes Radiotherapy Resistance in Medulloblastoma and Induces an Actionable Vulnerability to BET Inhibition.Cancer research · 2022Article
- Molecular Patho-mechanisms of cervical cancer (MMP1).Annals of medicine and surgery (2012) · 2022Review
- Ligands with different dimeric configurations potently activate the EphA2 receptor and reveal its potential for biased signaling.iScience · 2022Article
- Eph signaling is regulated by miRNA-210: Implications for corneal epithelial repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Regulation of the EphA2 receptor intracellular region by phosphomimetic negative charges in the kinase-SAM linker.Nature communications · 2021Article
- Ciliogenesis and autophagy are coordinately regulated by EphA2 in the cornea to maintain proper epithelial architecture.The ocular surface · 2021Article
- EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?Cancers · 2021Review
- EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway.BioMed research international · 2021Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
Receptor tyrosine kinases of the Eph family play multiple roles in the physiological regulation of tissue homeostasis and in the pathogenesis of various diseases, including cancer. The EphA2 receptor is highly expressed in most cancer cell types, where it has disparate activities that are not well understood. It has been reported that interplay of EphA2 with oncogenic signaling pathways promotes cancer cell malignancy independently of ephrin ligand binding and receptor kinase activity. In contrast, stimulation of EphA2 signaling with ephrin-A ligands can suppress malignancy by inhibiting the Ras-MAP kinase pathway, integrin-mediated adhesion, and epithelial to mesenchymal transition. Here we show that ephrin-A1 ligand-dependent activation of EphA2 decreases the growth of PC3 prostate cancer cells and profoundly inhibits the Akt-mTORC1 pathway, which is hyperactivated due to loss of the PTEN tumor suppressor. Our results do not implicate changes in the activity of Akt upstream regulators (such as Ras family GTPases, PI3 kinase, integrins, or the Ship2 lipid phosphatase) in the observed loss of Akt T308 and S473 phosphorylation downstream of EphA2. Indeed, EphA2 can inhibit Akt phosphorylation induced by oncogenic mutations of not only PTEN but also PI3 kinase. Furthermore, it can decrease the hyperphosphorylation induced by constitutive membrane-targeting of Akt. Our data suggest a novel signaling mechanism whereby EphA2 inactivates the Akt-mTORC1 oncogenic pathway through Akt dephosphorylation mediated by a serine/threonine phosphatase. Ephrin-A1-induced Akt dephosphorylation was observed not only in PC3 prostate cancer cells but also in other cancer cell types. Thus, activation of EphA2 signaling represents a possible new avenue for anti-cancer therapies that exploit the remarkable ability of this receptor to counteract multiple oncogenic signaling pathways.
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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.