Induction of E-cadherin endocytosis by loss of protein phosphatase 2A expression in human breast cancers

Biochem Biophys Res Commun. 2006 Oct 13;349(1):255-60. doi: 10.1016/j.bbrc.2006.08.037. Epub 2006 Aug 15.


The cell-cell adhesion molecule E-cadherin is stabilized by linking intracellularly with the actin cytoskeleton through PP2A-mediated recruitment of IQGAP1 to Rac1-bound E-cadherin-catenins complex in nonmalignant HME cells. However, little is known about the dysfunction of E-cadherin by loss or reduced expression of PP2A in human breast cancer cells. We report here that both human breast cancer MDA-MB-231 and MCF-7 cells were deficient in expression of the PP2A-A protein and lost the IQGAP1 recruitment to Rac1-bound catenins. In MDA-MB-231 cells, E-cadherin was also deficient. Immunohistochemical analysis of the normal-carcinoma matched human breast tissue arrays revealed that PP2A-A was expressed in 96% of normal tissue specimens but not in 57% of carcinoma specimens. Expression of E-cadherin in MCF-7 cells was 1.5-fold higher than that in HME cells, however, 80% of E-cadherin was endocytosed and incompletely anchored to F-actin. Therefore, we propose that the dysfunction of E-cadherin due to its endocytosis may occur in some proportion of human breast carcinomas in which the PP2A-A protein is lost or significantly reduced.

MeSH terms

  • Actins / chemistry
  • Biotinylation
  • Breast Neoplasms / metabolism*
  • Cadherins / metabolism*
  • Carcinoma / metabolism
  • Cell Adhesion
  • Cell Line, Tumor
  • Cytoskeleton / metabolism
  • Endocytosis
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Phosphoprotein Phosphatases / biosynthesis*
  • Protein Phosphatase 2
  • Tissue Distribution
  • ras GTPase-Activating Proteins / chemistry


  • Actins
  • Cadherins
  • IQ motif containing GTPase activating protein 1
  • ras GTPase-Activating Proteins
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2