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The transcriptional response to tumorigenic polarity loss in Drosophila

  1. Brandon D Bunker
  2. Tittu T Nellimoottil
  3. Ryan M Boileau
  4. Anne K Classen
  5. David Bilder  Is a corresponding author
  1. University of California, Berkeley, United States
  2. Department of Biological Sciences, United States
  3. Ludwig-Maximilians University, Germany
Research Article
  • Cited 45
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Cite this article as: eLife 2015;4:e03189 doi: 10.7554/eLife.03189

Abstract

Loss of polarity correlates with progression of epithelial cancers, but how plasma membrane misorganization drives oncogenic transcriptional events remains unclear. The polarity regulators of the Drosophila Scribble (Scrib) module are potent tumor suppressors and provide a model for mechanistic investigation. RNA profiling of Scrib mutant tumors reveals multiple signatures of neoplasia, including altered metabolism and dedifferentiation. Prominent among these is upregulation of cytokine-like Unpaired (Upd) ligands, which drive tumor overgrowth. We identified a polarity-responsive enhancer in upd3, which is activated in a coincident manner by both JNK-dependent Fos and aPKC-mediated Yki transcription. This enhancer, and Scrib mutant overgrowth in general, are also sensitive to activity of the Polycomb Group (PcG), suggesting that PcG attenuation upon polarity loss potentiates select targets for activation by JNK and Yki. Our results link epithelial organization to signaling and epigenetic regulators that control tissue repair programs, and provide insight into why epithelial polarity is tumor-suppressive.

Article and author information

Author details

  1. Brandon D Bunker

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tittu T Nellimoottil

    University of Southern California, Department of Biological Sciences, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ryan M Boileau

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Anne K Classen

    Department of Human Biology and Bioimaging, Ludwig-Maximilians University, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. David Bilder

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    bilder@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Helen McNeill, The Samuel Lunenfeld Research Institute, Canada

Publication history

  1. Received: July 11, 2014
  2. Accepted: February 25, 2015
  3. Accepted Manuscript published: February 26, 2015 (version 1)
  4. Version of Record published: March 23, 2015 (version 2)

Copyright

© 2015, Bunker et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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