ArticleCancer research2014
JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 80 citations in OpenAlex.
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- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Article
- EPHA2-Ephrin-B1 cis-interaction drives an oncogenic reverse signaling, leading to the recurrence of oral cancer.Cell communication and signaling : CCS · 2026Article
- EphA2 sustains the adaptive response of colorectal organoids to chemotherapy.Frontiers in cell and developmental biology · 2026Article
- Conversion of natural cytokine receptors into orthogonal synthetic biosensors.Nature chemical biology · 2025Article
- Regulation of Blood-Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer's Disease and Brain Tumors.Molecules (Basel, Switzerland) · 2025Review
- Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.World journal of gastrointestinal oncology · 2024Review
- Comprehensive analysis of Epha10 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in non-small cell lung cancer.Scientific reports · 2024Article
- The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.Cells · 2024Article
- The Role and Efficacy of JNK Inhibition in Inducing Lung Cancer Cell Death Depend on the Concentration of Cisplatin.ACS omega · 2024Article
- Exploring the potential of EphA2 receptor signaling pathway: a comprehensive review in cancer treatment.Molecular biology reports · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Cyclovirobuxine D inhibits growth and progression of non‑small cell lung cancer cells by suppressing the KIF11‑CDC25C‑CDK1‑CyclinB1 GInternational journal of oncology · 2023Article
- Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer.International journal of biological sciences · 2023Article
- Restored microRNA-519a enhances the radiosensitivity of non-small cell lung cancer via suppressing EphA2.Gene therapy · 2022Article
- Thymic epithelial cells require lipid kinase Vps34 for CD4 but not CD8 T cell selection.The Journal of experimental medicine · 2022Article
- Targeting cancer stemness mediated by BMI1 and MCL1 for non-small cell lung cancer treatment.Journal of cellular and molecular medicine · 2022Article
- Novel blood-based hypomethylation of SH3BP5 is associated with very early-stage lung adenocarcinoma.Genes & genomics · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Recent genome-wide analyses in human lung cancer revealed that EPHA2 receptor tyrosine kinase is overexpressed in non-small cell lung cancer (NSCLC), and high levels of EPHA2 correlate with poor clinical outcome. However, the mechanistic basis for EPHA2-mediated tumor promotion in lung cancer remains poorly understood. Here, we show that the JNK/c-JUN signaling mediates EPHA2-dependent tumor cell proliferation and motility. A screen of phospho-kinase arrays revealed a decrease in phospho-c-JUN levels in EPHA2 knockdown cells. Knockdown of EPHA2 inhibited p-JNK and p-c-JUN levels in approximately 50% of NSCLC lines tested. Treatment of parental cells with SP600125, a c-JUN-NH2-kinase (JNK) inhibitor, recapitulated defects in EPHA2-deficient tumor cells, whereas constitutively activated JNK mutants were sufficient to rescue phenotypes. Knockdown of EPHA2 also inhibited tumor formation and progression in xenograft animal models in vivo. Furthermore, we investigated the role of EPHA2 in cancer stem-like cells (CSC). RNA interference-mediated depletion of EPHA2 in multiple NSCLC lines decreased the ALDH(+) cancer stem-like population and tumor spheroid formation in suspension. Depletion of EPHA2 in sorted ALDH(+) populations markedly inhibited tumorigenicity in nude mice. Furthermore, analysis of a human lung cancer tissue microarray revealed a significant, positive association between EPHA2 and ALDH expression, indicating an important role for EPHA2 in human lung CSCs. Collectively, these studies revealed a critical role of JNK signaling in EPHA2-dependent lung cancer cell proliferation and motility and a role for EPHA2 in CSC function, providing evidence for EPHA2 as a potential therapeutic target in NSCLC. Cancer Res; 74(9); 2444-54. ©2014 AACR.
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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.