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Targeting a Galectin-3/EGR1 transcriptional complex inhibits the pro-metastatic signature in TRIM49-deficient gastric adenocarcinoma

GSE289465 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 18 samples 2025/09/17 GPL20301GPL23227
Summary
Distal metastasis, driven by intracellular signaling rewiring, is a leading cause of cancer mortality. The role of post-translational modifications in metastasis remains unclear. A CRISPR screen in a gastric adenocarcinoma (GAC) mouse model identified TRIM49 as a metastasis suppressor. TRIM49 is downregulated in most advanced GACs, correlating with poor prognosis. Galectin-3, stabilized in TRIM49-deficient cells due to impaired degradation, forms a complex with EGR1, enhancing pro-metastatic gene expression. Disrupting this complex with GB1107 inhibits metastasis in mouse models. The Galectin-3/EGR1 complex in TRIM49-deficient GAC is a key driver of metastasis and a potential therapeutic target.
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