N-cadherin mediates the migration of MCF-10A cells undergoing bone morphogenetic protein 4-mediated epithelial mesenchymal transition

Tumour Biol. 2015 May;36(5):3549-56. doi: 10.1007/s13277-014-2991-9. Epub 2014 Dec 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 4 / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Humans
  • Mammary Glands, Human / pathology
  • Morphogenesis / genetics
  • Neoplasm Metastasis
  • Zonula Occludens-1 Protein / genetics

Substances

  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Cadherins
  • TJP1 protein, human
  • Zonula Occludens-1 Protein