The transcriptional response to tumorigenic polarity loss in Drosophila
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 inve...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/03189 |
| _version_ | 1811180662982443008 |
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| author | Brandon D Bunker Tittu T Nellimoottil Ryan M Boileau Anne K Classen David Bilder |
| author_facet | Brandon D Bunker Tittu T Nellimoottil Ryan M Boileau Anne K Classen David Bilder |
| author_sort | Brandon D Bunker |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:05:53Z |
| format | Article |
| id | doaj.art-2c97bc4bab15425880942988bd125a83 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:53Z |
| publishDate | 2015-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-2c97bc4bab15425880942988bd125a832022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2015-02-01410.7554/eLife.03189The transcriptional response to tumorigenic polarity loss in DrosophilaBrandon D Bunker0Tittu T Nellimoottil1Ryan M Boileau2Anne K Classen3David Bilder4Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesUniversity of Southern California, Department of Biological Sciences, Los Angeles, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesLoss 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.https://elifesciences.org/articles/03189tumorcancerepithelial celltranscriptomepolarity |
| spellingShingle | Brandon D Bunker Tittu T Nellimoottil Ryan M Boileau Anne K Classen David Bilder The transcriptional response to tumorigenic polarity loss in Drosophila eLife tumor cancer epithelial cell transcriptome polarity |
| title | The transcriptional response to tumorigenic polarity loss in Drosophila |
| title_full | The transcriptional response to tumorigenic polarity loss in Drosophila |
| title_fullStr | The transcriptional response to tumorigenic polarity loss in Drosophila |
| title_full_unstemmed | The transcriptional response to tumorigenic polarity loss in Drosophila |
| title_short | The transcriptional response to tumorigenic polarity loss in Drosophila |
| title_sort | transcriptional response to tumorigenic polarity loss in drosophila |
| topic | tumor cancer epithelial cell transcriptome polarity |
| url | https://elifesciences.org/articles/03189 |
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