ArticleCell death & disease2018
EPH receptor A2 governs a feedback loop that activates Wnt/β-catenin signaling in gastric cancer.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- A WISPer of Hope? WISP2 and Vasculogenic Mimicry in Gastric Cancer-Implications for EMT and Tumor Plasticity.Digestive diseases and sciences · 2026Article
- Unlocking the potential of EphA2 with precision-guided cancer therapy: bicycle drug conjugates.Journal of translational medicine · 2026Review
- The EphA3 Antibody Enhances CD47 Antibody-Mediated Phagocytosis by Repolarizing M2-Like Tumor-Associated Macrophages in a Preclinical Model of Recurrent Head and Neck Cancer.OncoTargets and therapy · 2026Article
- SRSF9 mediates oncogenic RNA splicing of SLC37A4 via liquid-liquid phase separation to promote oral cancer progression.Journal of advanced research · 2026Article
- DDX1 facilitates lenvatinib resistance in hepatocellular carcinoma through regulating ephrin-A3 and activating the Wnt/β-catenin signaling pathway.Functional & integrative genomics · 2025Article
- Loss of primary cilia promotes EphA2-mediated endothelial-to-mesenchymal transition in the ovarian tumor microenvironment.Molecular oncology · 2025Article
- Immunological role and prognostic value of ITGA3 and ITGA5 in oral squamous cell carcinoma.Scientific reports · 2025Article
- The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma.Epigenomics · 2025Review
- Liquid-liquid phase separation in cell physiology and cancer biology: recent advances and therapeutic implications.Frontiers in oncology · 2025Review
- Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity.Cell communication and signaling : CCS · 2024Review
- ARID1A loss induces P4HB to activate fibroblasts to support lung cancer cell growth, invasion, and chemoresistance.Cancer science · 2024Article
- Emerging Roles of YES1 in Cancer: The Putative Target in Drug Resistance.International journal of molecular sciences · 2024Review
- HPV E6/E7: insights into their regulatory role and mechanism in signaling pathways in HPV-associated tumor.Cancer gene therapy · 2024Review
- Advances and current concepts on Eph receptors and ephrins in upper digestive tract cancers.Frontiers in oncology · 2024Review
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- A comprehensive insight into the correlation between ncRNAs and the Wnt/β-catenin signalling pathway in gastric cancer pathogenesis.Cell communication and signaling : CCS · 2023Review
- The EPH/Ephrin System in Pancreatic Ductal Adenocarcinoma (PDAC): From Pathogenesis to Treatment.International journal of molecular sciences · 2023Review
- Molecular Patho-mechanisms of cervical cancer (MMP1).Annals of medicine and surgery (2012) · 2022Review
- ALW-II-41-27, an EphA2 inhibitor, inhibits proliferation, migration and invasion of cervical cancer cells via inhibition of the RhoA/ROCK pathway.Oncology letters · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The erythropoietin-producing hepatoma (EPH) receptor A2 (EphA2) belongs to the Eph family of receptor tyrosine kinases. EphA2 is highly correlated with the formation of many solid tumors and has been linked to the dysregulation of signaling pathways that promote tumor cell proliferation, migration, and invasion as well as angiogenesis. Deregulation of Wnt signaling is implicated in many forms of human disease including gastric cancer. We previously reported that EphA2 promotes the epithelial-mesenchymal transition through Wnt/β-catenin signaling in gastric cancer. Herein, we present a novel mechanism by which EphA2 regulates Wnt/β-catenin signaling. EphA2 acts as a receptor for Wnt ligands and recruits Axin1 to the plasma membrane by directly binding Dvl2. The EphA2-Dvl2/Axin1 interaction was enhanced by Wnt3a treatment, suggesting that EphA2 acts as a functional receptor for the Wnt/β-catenin pathway and plays a vital role in downstream signaling. We showed that Dvl2 mediates the EphA2-Axin1 interaction by binding to the tyrosine kinase domain of EphA2. We propose that EphA2/Dvl2/Axin1 forms a complex that destabilizes the β-catenin destruction complex and allows β-catenin to translocate to the nucleus and initiate the transcription of c-MYC, the primary Wnt signaling target gene. Intriguingly, c-MYC could bind directly to the EphA2 and Wnt1 promoter to enhance their transcription. The entire process formed an EphA2-mediated feed-forward loop. A small molecular inhibitor of EphA2 potently inhibited the proliferation of gastric cancer in vitro and in vivo, including gastric cancer patient-derived xenografts. Thus, our data identify EphA2 as an excellent candidate for gastric cancer 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.