title: MT2-MMP induces proteolysis and leads to EMT in carcinomas.
abstract: Epithelial-mesenchymal transition (EMT) is critical for carcinoma invasiveness and metastasis. To investigate the role of membrane-type-2 matrix metalloproteinase (MT2-MMP) in EMT, we generated lentiviral constructs of wild-type (WT) and an inactive Glu260Ala (E260A) mutant MT2-MMP and derived stably transfected HCT116 and A549 cell lines. WT-transfected cells appeared mesenchymal-like, whereas cells transfected with the E260A mutant were epithelial-like, as were cells treated with an MMP inhibitor (GM6001). Expression of E-cadherin, β-catenin, and zonula occludens-1 was lower in cells transfected with WT MT2-MMP compared to vector controls, cells treated with GM6001, or cells transfected with the E260A mutant. An 80-kD N-terminal fragment of E-cadherin was immunoprecipitated in conditioned medium from WT MT2-MMP cells, but not in the medium from vector controls, cells treated with GM6001, or E260A mutant cells. When endogenous expression of MT2-MMP in A2780 human ovarian cancer cells was inhibited using GM6001 or MT2-MMP-specific siRNA, levels of the 80-kD E-cadherin fragment in conditioned medium were decreased. Chick embryo chorioallantoic membrane invasion assays demonstrated that cells transfected with WT MT2-MMP were more invasive than cells transfected with control vector, treated with GM6001, or transfected with the E260A mutant. These results suggest that MT2-MMP degrades adherens and tight junction proteins and results in EMT, making it a potential mediator of EMT in carcinomas.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Heilongjiang Province Hospital, Harbin, China.
authors.forename: Jinfa
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Deng
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
authors.forename: Bokang
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China.
authors.forename: Changlian
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000072283:A549 Cells; D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D045325:HCT116 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D053517:Matrix Metalloproteinase 15 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D059748:Proteolysis; D014162:Transfection
chemical_list: C507098:MMP15 protein, human; D053517:Matrix Metalloproteinase 15
keywords: E-cadherin; MT2-MMP; cancer; epithelial-mesenchymal transition (EMT); zonula occludens-1 (ZO-1)