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.
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Acknowledgements
We would like to thank members of the Muthuswamy laboratory for all their input and helpful discussions. We thank M. Zaratiegui for statistical analysis and interpretation and ARIAD pharmaceutical for the synthetic dimerizing ligand, AP1510. S.K.M. was supported by CA098830 from the National Cancer Institute (NCI), The V foundation Scholar award, Rita Allen Scholar award, Find a Cure Today (FACT), Glencove cares and Long Islanders Against Breast Cancer (LIBC) foundation. T.P. was supported by NCI Canada. T.H. was supported by a fellowship from the Department of Defense (DAMD17-03-1-0194). M.E.N. was also supported by a fellowship from the Department of Defense (DAMD17-03-0193). We dedicate this work to the memory of our friend and colleague, Teresa Haire.
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Aranda, V., Haire, T., Nolan, M. et al. Par6–aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nat Cell Biol 8, 1235–1245 (2006). https://doi.org/10.1038/ncb1485
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DOI: https://doi.org/10.1038/ncb1485
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