Article abstract
Nature Cell Biology 8, 1235 - 1245 (2006)
Published online: 22 October 2006 | doi:10.1038/ncb1485
Par6–aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control
Victoria Aranda1,7, Teresa Haire1,2,7, Marissa E. Nolan1,3, Joseph P. Calarco4,6, Avi Z. Rosenberg1,3, James P. Fawcett5, Tony Pawson5 & Senthil K. Muthuswamy1,2,3,4
Abstract
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.
- Cold Spring Harbor Laboratory,One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
- Department of Molecular Genetics and Microbiology, Stony Brook University, NY 11794, USA.
- Graduate Program in Genetics, Stony Brook University, NY 11794, USA.
- Watson School of Biological Sciences, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
- Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600, University Avenue, University of Toronto, Toronto, Ontario, M5G 1X5, Canada.
- Department of Chemistry, University of Toronto, 80 Saint George St. Toronto M5S 3H6, Canada.
- These authors contributed equally to this work.
Correspondence to: Senthil K. Muthuswamy1,2,3,4 e-mail: muthuswa@cshl.edu
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