ArticleCell death & disease2022
Blocking STAT3 signaling augments MEK/ERK inhibitor efficacy in esophageal squamous cell carcinoma.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Differential expression, activity, and fibroblast growth factor 2-mediated modulation of purine-metabolizing enzymes in cultured cortical astrocytes and microglia.Purinergic signalling · 2026Article
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- Chinese Expert Consensus for the Application of rh-aFGF for Chronic Refractory Wounds.Pharmaceuticals (Basel, Switzerland) · 2026Article
- PD0325901 alleviates thrombin-inhibited osteogenic differentiation through an IL-1β-activated feedback loop between MEK-Erk1/2 and NF-κB signal pathways: insights from bioinformatics and experimental verification.Frontiers in immunology · 2026Article
- Construction of circadian clock signature for tumor microenvironment in predicting survival of esophageal squamous cell carcinoma.Frontiers in immunology · 2026Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Interpretable prediction of drug synergy for breast cancer by random forest with features from Boolean modeling of signaling pathways.Scientific reports · 2025Article
- STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRASCancer science · 2025Article
- Evaluating the specific STAT3 inhibitor YHO-1701 in ovarian cancer cell lines and patient-derived cell models: efficacy, mechanisms, and therapeutic potential.Journal of gynecologic oncology · 2025Article
- Review
- Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma.Journal of inflammation research · 2025Review
- NIR-715 photodynamic therapy induces immunogenic cancer cell death by enhancing the endoplasmic reticulum stress response.Cell death & disease · 2024Article
- Neuroprotective Effects of STAT3 Inhibitor on Hydrogen Peroxide-Induced Neuronal Cell Death via the ERK/CREB Signaling Pathway.Neurochemical research · 2024Article
- Targeting Stem Cells and Dysplastic Features With Dual MEK/ERK and STAT3 Suppression in Gastric Carcinogenesis.Gastroenterology · 2024Article
- Epstein-Barr virus-encoded miR-BART11-3p modulates the DUSP6-MAPK axis to promote gastric cancer cell proliferation and metastasis.Journal of virology · 2023Article
- MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas.Nature communications · 2023Article
- Targeting IGF1R signaling enhances the sensitivity of cisplatin by inhibiting proline and arginine metabolism in oesophageal squamous cell carcinoma under hypoxia.Journal of experimental & clinical cancer research : CR · 2023Article
- Cyclic tensile force modifies calvarial osteoblast function via the interplay between ERK1/2 and STAT3.BMC molecular and cell biology · 2023Article
- A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors.Open medicine (Warsaw, Poland) · 2023Article
- Single-Cell Transcriptomics of Endothelial Cells in Upper and Lower Human Esophageal Squamous Cell Carcinoma.Current oncology (Toronto, Ont.) · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the world's leading causes of death, and its primary clinical therapy relies on surgical resection, chemotherapy, radiotherapy, and chemoradiotherapy. Although the genomic features and clinical significance of ESCC have been identified, the outcomes of targeted therapies are still unsatisfactory. Here, we demonstrate that mitogen-activated protein kinase (MAPK) signaling is highly activated and associated with poor prognosis in patients with ESCC. Mitogen-activated protein kinase kinase (MEK) inhibitors efficiently blocked the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in ESCC, while signal transducer and activator of transcription 3 (STAT3) signaling was rapidly activated. Combined STAT3 inhibition prevented the emergence of resistance and enhanced MEK inhibitor-induced cell cycle arrest and senescence in vitro and in vivo. Mechanistic studies revealed that the suppressor of cytokine signaling 3 (SOCS3) was downregulated, resulting in an increase in STAT3 phosphorylation in MEK-inhibited cells. Furthermore, chromatin immunoprecipitation showed that ELK1, which was activated by MEK/ERK signaling, induced SOCS3 transcription. These data suggest that the development of combined MEK and STAT3 inhibition could be a useful strategy in ESCC targeted 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.