The transcriptional response to tumorigenic polarity loss in Drosophila

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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.

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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.
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.
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.
Anne K Classen

Department of Human Biology and Bioimaging, Ludwig-Maximilians University, Munich, Germany

Competing interests
The authors declare that no competing interests exist.
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.

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