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Citation
Bunker, B.D., Nellimoottil, T.T., Boileau, R.M., Classen, A.K., Bilder, D. (2015). The transcriptional response to tumorigenic polarity loss in Drosophila.  eLife 4(): e03189.
FlyBase ID
FBrf0227898
Publication Type
Research paper
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.
PubMed ID
PubMed Central ID
PMC4369581 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    eLife
    Title
    eLife
    ISBN/ISSN
    2050-084X
    Data From Reference
    Aberrations (1)
    Alleles (37)
    Genes (28)
    Human Disease Models (4)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (28)