title: N-cadherin mediates the migration of MCF-10A cells undergoing bone morphogenetic protein 4-mediated epithelial mesenchymal transition.
abstract: 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.
authors.affiliation: East-West Medical Research Institute/College of Medicine, Kyung Hee University, Seoul, 130-701, Korea, kisookpark@khu.ac.kr.
authors.forename: Ki-Sook
authors.initials: KS
authors.lastname: Park
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Dubon
authors.forename: Barry M
authors.initials: BM
authors.lastname: Gumbiner
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000473:pathology; D009024:Morphogenesis / Q000235:genetics; D009362:Neoplasm Metastasis; D062826:Zonula Occludens-1 Protein / Q000235:genetics
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D015820:Cadherins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein