Targeting a Galectin-3/EGR1 transcriptional complex inhibits the pro-metastatic signature in TRIM49-deficient gastric adenocarcinoma
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. Overall design: Cut&Tag of EGR1 and Galectin-3 to identify the binding sites of key genes; RNA-Seq of inhibition of Galectin-3 and overexpression of TRIM49 for identifying their targets.