N-cadherin mediates the migration of MCF-10A cells undergoing bone morphogenetic protein 4-mediated epithelial mesenchymal transition.
N-cadherin mediates the migration of MCF-10A cells undergoing bone morphogenetic protein 4-mediated epithelial mesenchymal transition.
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N-钙粘蛋白介导 MCF-10A 细胞的迁移，经历骨形态发生蛋白 4 介导的上皮间质转化。
DOI：
10.1007/s13277-014-2991-9
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Gumbiner,BarryM
中科院分区：
文献类型：
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作者：
Park,Ki-Sook;Dubon,MariaJose;Gumbiner,BarryM
乳腺上皮细胞的上皮-间质转化（EMT）在乳腺正常形态发生和乳腺癌转移中起重要作用。钙粘蛋白从E-钙粘蛋白到N-钙粘蛋白的转变在EMT中发挥着重要作用。我们发现钙粘蛋白转换在骨形态发生蛋白4（BMP 4）诱导的MCF-10A细胞EMT中是重要的。BMP 4可增加MCF-10A细胞中SMAD蛋白的磷酸化。典型的BMP 4信号降低了MCF-10A细胞中E-钙粘蛋白的表达，并破坏了紧密连接蛋白ZO-1的极性。BMP-4处理MCF-10A细胞后，N-cadherin和SNAI 2表达上调。当使用三维培养分析评估时，表达N-钙粘蛋白的MCF-10A细胞响应于BMP 4迁移到I型胶原凝胶中。因此，活性典型BMP 4信号传导对于乳腺上皮细胞的迁移和EMT是重要的。此外，E-cadherin的减少和/或N-cadherin的增加可能是BMP 4诱导的迁移和EMT所必需的。
Epithelial–mesenchymal transition (EMT) of mammary epithelial cells is important in both normal morphogenesis of mammary glands and metastasis of breast cancer. Cadherin switching from E-cadherin to N-cadherin plays important roles in EMT. We found that cadherin switching is important in bone morphogenetic protein 4 (BMP4)-induced EMT in MCF-10A cells. BMP4 increased the phosphorylation of SMAD proteins in MCF-10A cells. Canonical BMP4 signaling decreased the expression of E-cadherin and disrupted the polarity of the tight junction protein ZO-1 in MCF-10A cells. However, the expression of N-cadherin and SNAI2 was up-regulated in BMP4-treated MCF-10A cells. MCF-10A cells that expressed N-cadherin migrated into type I collagen gels in response to BMP4 when evaluated using three-dimensional culture assays. Thus, active canonical BMP4 signaling is important for the migration and EMT of mammary epithelial cells. Moreover, the decrease in E-cadherin and/or increase in N-cadherin may be required for BMP4-induced migration and EMT.