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2017 ; 10
(ä): 2837-2847
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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): 2837-2847
PMID28652766
show 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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