ST7 binds YBX1 to suppress MMP14 expression and inhibit metastasis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a major contributor to cancer-related deaths globally. The mechanisms of NSCLC metastasis, largely driven by epithelial-mesenchymal transition (EMT), remain incompletely understood. The Cancer Genome Atlas - Lung Adenocarcinoma (TCGA-LUAD) dataset analysis revealed that suppression of tumorigenicity 7 (ST7) may play a role in preventing the EMT process and metastasis in NSCLC. In this study, we revealed that ST7 suppressed the expression of Matrix metalloproteinase 14 (MMP14) by binding Y-box binding protein 1 (YBX1) and blocking its nuclear translocation. Consequently, ST7 silencing enhanced both EMT and metastatic progression in NSCLC experimental models, including A549 and H1299 cell lines in vitro and a tail-vein lung metastasis model in BALB/c nude mice in vivo. Collectively, our results revealed a novel ST7/YBX1/MMP14 signaling axis that might be targeted in NSCLC metastasis.