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Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Onco+Targets+Ther 2017 ; 10 (ä): 2837-47 Nephropedia Template TP
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Role of matrix metalloproteinase-9 in transforming growth factor-?1-induced epithelial?mesenchymal transition in esophageal squamous cell carcinoma #MMPMID28652766
Bai X; Li Yy; Zhang Hy; Wang F; He Hl; Yao Jc; Liu L; Li Ss
Onco Targets Ther 2017[]; 10 (ä): 2837-47 PMID28652766show ga
Epithelial?mesenchymal transition (EMT) is thought to be a crucial event during the early metastasis of tumor cells. Transforming growth factor (TGF)-?1 is involved in the process of EMT in a variety of human malignancies. Matrix metalloproteinase (MMP)-9 plays an important role in tumor invasion and metastasis, and its expression is regulated by various growth factors, including TGF-?1, in different cell types. To date, the role of MMP-9 in TGF-?1-induced EMT in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to elucidate the mechanism underlying MMP-9-mediated TGF-?1 induction of EMT in ESCC. We analyzed the expression of MMP-9, E-cadherin, and vimentin, in ESCC cells (EC-1), before and after the treatment with exogenous TGF-?1 or a broad spectrum MMP inhibitor, GM6001. Additionally, we analyzed the activity of MMP-9 in these cells and performed MMP-9 knockdown experiments. The results obtained in this study demonstrated that the treatment of EC-1 cells with TGF-?1 can induce EMT, together with the upregulation of vimentin and downregulation of E-cadherin expression in a time-dependent manner. The treatment with GM6001 was shown to attenuate TGF-?1-induced EMT. Furthermore, the exposure of EC-1 cells to TGF-?1 increased the expression and activity of MMP-9, while MMP-9 knockdown blocked TGF-?1-induced EMT and inhibited cell invasiveness and migration. Additionally, treatment with the recombinant human MMP-9 was shown to induce EMT and enhance ESCC cell invasion and metastasis. The obtained data suggest that the regulation of MMP-9 by TGF-?1 may represent a novel mechanism underlying TGF-?1-induced EMT in ESCC.
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Onco+Targets+Ther 2017 ; 10 (ä): 2837-47
