N-cadherin mediates the migration of MCF-10A cells undergoing bone morphogenetic protein 4-mediated epithelial mesenchymal transition
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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.
KeywordsEpithelial mesenchymal transition Bone morphogenetic protein 4 N-cadherin Mammary epithelial cell MCF-10A
This work was financially supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C1479 to Ki-Sook Park), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2012R1A1A2042265 to Ki-Sook Park), a grant from Kyung Hee University in 2014 (KHU-20140698 to Ki-Sook Park), and National Institutes of Health grant R01 (GM-28140 to Barry Gumbiner).
Conflicts of interest
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