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ST7 binds YBX1 to suppress MMP14 expression and inhibit metastasis in non-small cell lung cancer
Yang Qin1, Yahan Chen1, Qian Cao1
1Department of Radiology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan 430050, China.
Abstract:
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.
Insights
Suppression of tumorigenicity 7 (ST7) inhibits non-small cell lung cancer (NSCLC) metastasis by blocking Matrix metalloproteinase 14 (MMP14) expression via Y-box binding protein 1 (YBX1). ST7 silencing accelerates EMT and metastasis in NSCLC models.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide.
- Epithelial-mesenchymal transition (EMT) is a key driver of NSCLC metastasis, but its regulatory mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of Suppression of tumorigenicity 7 (ST7) in regulating NSCLC metastasis.
- To elucidate the molecular mechanisms by which ST7 influences EMT and cancer cell invasion.
Main Methods:
- Analysis of The Cancer Genome Atlas - Lung Adenocarcinoma (TCGA-LUAD) dataset.
- In vitro studies using NSCLC cell lines (A549, H1299) with ST7 silencing.
- In vivo experiments using a tail-vein lung metastasis model in BALB/c nude mice.
- Investigation of the interaction between ST7, Y-box binding protein 1 (YBX1), and Matrix metalloproteinase 14 (MMP14).
Main Results:
- ST7 was identified as a potential inhibitor of EMT and metastasis in NSCLC.
- ST7 directly binds to YBX1, preventing its nuclear translocation and subsequently suppressing MMP14 expression.
- Silencing of ST7 promoted EMT and enhanced metastatic progression in both in vitro and in vivo NSCLC models.
- A novel ST7/YBX1/MMP14 signaling axis was identified.
Conclusions:
- The ST7/YBX1/MMP14 axis represents a novel regulatory pathway in NSCLC metastasis.
- Targeting this signaling axis may offer a potential therapeutic strategy for inhibiting NSCLC progression and metastasis.
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