Membrane type 1-matrix metalloproteinase induces epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma: Observations from clinical and in vitro analyses

Lijuan Pang, Qiuxiang Li, Shugang Li, Jianwei He, Weiwei Cao, Jiaojiao Lan, Bin Sun, Hong Zou, Chengyan Wang, Ruixue Liu, Cuilei Wei, Yutao Wei, Yan Qi, Jianming Hu, Weihua Liang, Wen Jie Zhang, Mei Wan, Feng Li

Research output: Contribution to journalArticle

Abstract

Membrane type 1-matrix metalloproteinase (MT1-MMP) is associated with enhanced tumorigenicity in many cancers. A recent study has revealed that MT1-MMP induces epithelial-to-mesenchymal transition (EMT) in prostate and breast cancer cells. However, its role in esophageal squamous cell carcinoma (ESCC) has not been studied. Here, we investigated the role of MT1-MMP in the dissemination of ESCC. Expression of MT1-MMP was detected by immunohistochemistry and tissue microarray in 88 Kazakh ESCC patients. Western blotting was performed to detect endogenous and overexpressed exogenous MT1-MMP in the Eca109 and Eca9706 cell lines, respectively. Transwell assay was used to estimate MT1-MMP-induced invasion and metastasis. EMT-associated proteins were detected by immunohistochemistry and western blotting. The associations between the expression of MT1-MMP and EMT-associated proteins with clinicopathologic parameters were analyzed. Overexpression of MT1-MMP was confirmed in Kazakh ESCC patients. MT1-MMP levels were found to be correlated with the depth of tumor infiltration. MT1-MMP induced EMT in ESCC both in vivo and in vitro, N-cadherin and Vimentin expression was upregulated upon MT1-MMP transfection into cells. However, E-cadherin was found to be downregulated. MT1-MMP-induced EMT led to increase migration and invasion in ESCC cell lines. In conclusion, our results suggest that MT1-MMP promotes ESCC invasion and metastasis.

Original languageEnglish (US)
Article number22179
JournalScientific Reports
Volume6
DOIs
StatePublished - Feb 26 2016

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Matrix Metalloproteinase 14
Epithelial-Mesenchymal Transition
Cadherins
Esophageal Squamous Cell Carcinoma
In Vitro Techniques
Western Blotting
Immunohistochemistry
Neoplasm Metastasis
Cell Line
Vimentin
Transfection

ASJC Scopus subject areas

  • General

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Membrane type 1-matrix metalloproteinase induces epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma : Observations from clinical and in vitro analyses. / Pang, Lijuan; Li, Qiuxiang; Li, Shugang; He, Jianwei; Cao, Weiwei; Lan, Jiaojiao; Sun, Bin; Zou, Hong; Wang, Chengyan; Liu, Ruixue; Wei, Cuilei; Wei, Yutao; Qi, Yan; Hu, Jianming; Liang, Weihua; Zhang, Wen Jie; Wan, Mei; Li, Feng.

In: Scientific Reports, Vol. 6, 22179, 26.02.2016.

Research output: Contribution to journalArticle

Pang, L, Li, Q, Li, S, He, J, Cao, W, Lan, J, Sun, B, Zou, H, Wang, C, Liu, R, Wei, C, Wei, Y, Qi, Y, Hu, J, Liang, W, Zhang, WJ, Wan, M & Li, F 2016, 'Membrane type 1-matrix metalloproteinase induces epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma: Observations from clinical and in vitro analyses', Scientific Reports, vol. 6, 22179. https://doi.org/10.1038/srep22179
Pang, Lijuan ; Li, Qiuxiang ; Li, Shugang ; He, Jianwei ; Cao, Weiwei ; Lan, Jiaojiao ; Sun, Bin ; Zou, Hong ; Wang, Chengyan ; Liu, Ruixue ; Wei, Cuilei ; Wei, Yutao ; Qi, Yan ; Hu, Jianming ; Liang, Weihua ; Zhang, Wen Jie ; Wan, Mei ; Li, Feng. / Membrane type 1-matrix metalloproteinase induces epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma : Observations from clinical and in vitro analyses. In: Scientific Reports. 2016 ; Vol. 6.
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AU - He, Jianwei

AU - Cao, Weiwei

AU - Lan, Jiaojiao

AU - Sun, Bin

AU - Zou, Hong

AU - Wang, Chengyan

AU - Liu, Ruixue

AU - Wei, Cuilei

AU - Wei, Yutao

AU - Qi, Yan

AU - Hu, Jianming

AU - Liang, Weihua

AU - Zhang, Wen Jie

AU - Wan, Mei

AU - Li, Feng

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AB - Membrane type 1-matrix metalloproteinase (MT1-MMP) is associated with enhanced tumorigenicity in many cancers. A recent study has revealed that MT1-MMP induces epithelial-to-mesenchymal transition (EMT) in prostate and breast cancer cells. However, its role in esophageal squamous cell carcinoma (ESCC) has not been studied. Here, we investigated the role of MT1-MMP in the dissemination of ESCC. Expression of MT1-MMP was detected by immunohistochemistry and tissue microarray in 88 Kazakh ESCC patients. Western blotting was performed to detect endogenous and overexpressed exogenous MT1-MMP in the Eca109 and Eca9706 cell lines, respectively. Transwell assay was used to estimate MT1-MMP-induced invasion and metastasis. EMT-associated proteins were detected by immunohistochemistry and western blotting. The associations between the expression of MT1-MMP and EMT-associated proteins with clinicopathologic parameters were analyzed. Overexpression of MT1-MMP was confirmed in Kazakh ESCC patients. MT1-MMP levels were found to be correlated with the depth of tumor infiltration. MT1-MMP induced EMT in ESCC both in vivo and in vitro, N-cadherin and Vimentin expression was upregulated upon MT1-MMP transfection into cells. However, E-cadherin was found to be downregulated. MT1-MMP-induced EMT led to increase migration and invasion in ESCC cell lines. In conclusion, our results suggest that MT1-MMP promotes ESCC invasion and metastasis.

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