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The epithelial polarity program: machineries involved and their hijacking by cancer

Oncogene volume 27, pages 6939–6957 (2008)Cite this article

Abstract

The Epithelial Polarity Program (EPP) adapts and integrates three ancient cellular machineries to construct an epithelial cell. The polarized trafficking machinery adapts the cytoskeleton and ancestral secretory and endocytic machineries to the task of sorting and delivering different plasma membrane (PM) proteins to apical and basolateral surface domains. The domain-identity machinery builds a tight junctional fence (TJ) between apical and basolateral PM domains and adapts ancient polarity proteins and polarity lipids on the cytoplasmic side of the PM, which have evolved to perform a diversity of polarity tasks across cells and species, to provide ‘identity’ to each epithelial PM domain. The 3D organization machinery utilizes adhesion molecules as positional sensors of other epithelial cells and the basement membrane and small GTPases as integrators of positional information with the activities of the domain-identity and polarized trafficking machineries. Cancer is a disease mainly of epithelial cells (90% of human cancers are carcinomas that derive from epithelial cells) that hijacks the EPP machineries, resulting in loss of epithelial polarity, which often correlates in extent with the aggressiveness of the tumor. Here, we review how the EPP integrates its three machineries and the strategies used by cancer to hijack them.

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Acknowledgements

We thank Aparna Lakkaraju for her artistic support and Marcelino Cereijido for useful comments on the manuscript. This study was supported by NIH Grants GM 34107 and EY08538 to ERB, by the Dyson Foundation and by the Research to Prevent Blindness Foundation.

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Authors and Affiliations

  1. Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, NY, USA

    B Tanos & E Rodriguez-Boulan

  2. Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA

    E Rodriguez-Boulan

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  1. B Tanos
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  2. E Rodriguez-Boulan
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Correspondence to E Rodriguez-Boulan.

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Tanos, B., Rodriguez-Boulan, E. The epithelial polarity program: machineries involved and their hijacking by cancer. Oncogene 27, 6939–6957 (2008). https://doi.org/10.1038/onc.2008.345

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  • DOI: https://doi.org/10.1038/onc.2008.345

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