ArticleCell death & disease2025
EGR4 transcriptionally upregulates GDF15 to promote gastric cancer metastasis.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Gastric cancer (GC) metastasis remains a major cause of poor prognosis, yet its molecular drivers are poorly understood. Here, we integrated single-cell RNA sequencing (scRNA-seq) of primary tumors and matched metastatic lymph nodes from six GC patients to identify a metastatic epithelial subpopulation characterized by EGR4 overexpression. Kaplan-Meier analysis revealed that high EGR4 expression correlated with reduced survival in GC patients. Mechanistically, chromatin immunoprecipitation sequencing (ChIP-seq) and luciferase assays demonstrated that EGR4 directly bound to the GDF15 promoter, driving its transcriptional activation. Functional studies showed that EGR4 promoted migration and metastasis via GDF15-mediated ErbB3/ErbB1 hetero-dimerization, which activated PI3K/AKT and MAPK/ERK pathways. Furthermore, CellChat analysis identified robust interactions between EGR4
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