title: Membrane type 1-matrix metalloproteinase induces epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma: Observations from clinical and in vitro analyses.
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.
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Qiuxiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Public Health, Medical School, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Lan
authors.affiliation: Department of Stomatology, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Cuilei
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
authors.forename: Wen Jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Wan
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.|Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology*; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014746:Vimentin; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14