MT2-MMP induces proteolysis and leads to EMT in carcinomas

作者：Liu, Yusi; Sun, Xiaojiao; Feng, Jinfa; Deng, Li-Li; Liu, Yihao; Li, Bokang; Zhu, Mingyue; Lu, Changlian^*; Zhou, Lingyun^*

来源：Oncotarget, 2016, 7(30): 48193-48205.

DOI：10.18632/oncotarget.10194

• MT2-MMP
• cancer
• epithelial-mesenchymal transition (EMT)
• E-cadherin
• zonula occludens-1 (ZO-1)

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, beta-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.

• 出版日期2016-7-26
• 单位哈尔滨医科大学; 黑龙江省医院