Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control

Nat Cell Biol. 2006 Nov;8(11):1235-45. doi: 10.1038/ncb1485. Epub 2006 Oct 22.


The polarized glandular organization of epithelial cells is frequently lost during development of carcinoma. However, the specific oncogene targets responsible for polarity disruption have not been identified. Here, we demonstrate that activation of ErbB2 disrupts apical-basal polarity by associating with Par6-aPKC, components of the Par polarity complex. Inhibition of interaction between Par6 and aPKC blocked the ability of ErbB2 to disrupt the acinar organization of breast epithelia and to protect cells from apoptosis but was not required for cell proliferation. Therefore, oncogenes target polarity proteins to disrupt glandular organization and protect cells from apoptotic death during development of carcinoma.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carrier Proteins / metabolism*
  • Cell Cycle / physiology
  • Cell Line
  • Cell Polarity / physiology
  • Cell Proliferation*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Gene Expression
  • Immunoblotting
  • Immunoprecipitation
  • Microscopy, Fluorescence
  • Protein Binding
  • Protein Kinase C / metabolism*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction / physiology


  • Carrier Proteins
  • Receptor, ErbB-2
  • PKC-3 protein
  • Protein Kinase C