Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer

Am J Pathol. 2004 Jun;164(6):2269-78. doi: 10.1016/S0002-9440(10)63783-2.

Abstract

In a search for signaling molecules that act downstream of E-cadherin inactivation in cancer, we examined the expression and localization of E-cadherin-associated proteins in lobular carcinoma, in which the E-cadherin gene is frequently inactivated, and found that E-cadherin down-regulation correlated with the cytoplasmic localization of p120ctn. Similar cytoplasmic localization of p120ctn and growth factor-induced accumulation of tyrosine-phosphorylated p120ctn in the protrusive domain were observed in E-cadherin-deficient breast cancer cells. Down-regulation of endogenous p120ctn by RNA interference promoted stress fiber formation and induced a flattened morphology with an increase of Rho-GTPase activity; it also reduced the development of membranous protrusions and migratory activity in E-cadherin-deficient breast cancer cells. Inactivation of E-cadherin in cancer cells is associated with the conversion from epithelial to mesenchymal phenotype, which also occurs in physiological conditions such as developmental processes. Cytoplasmic localization of p120ctn accompanied by E-cadherin down-regulation was observed in mesoderm cells that had undergone epithelial-mesenchymal transition during early mouse embryogenesis. Collectively, our results suggest that cytoplasmic p120ctn may contribute to the invasive phenotype of E-cadherin-deficient breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cadherins / genetics
  • Cadherins / physiology*
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / pathology
  • Catenins
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / genetics*
  • Cell Division
  • Cell Movement
  • Female
  • Humans
  • Immunohistochemistry
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology*
  • Oligodeoxyribonucleotides
  • Phosphoproteins / analysis
  • Phosphoproteins / genetics*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Plasmids
  • RNA, Small Interfering / genetics
  • Transfection

Substances

  • Cadherins
  • Catenins
  • Cell Adhesion Molecules
  • Oligodeoxyribonucleotides
  • Phosphoproteins
  • RNA, Small Interfering
  • delta catenin
  • Phosphotyrosine