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Project grant

Using the Drosophila fly intestine to investigate Wnt targets in vivo

A sideways shot of a drosophila

At a glance

Completed
Award date
November 2010 - November 2013
Grant amount
£350,525
Principal investigator
Dr Owen Sansom
Institute
University of Glasgow

R

  • Replacement
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Contents

Application abstract

The Apc tumour suppressor gene is mutated in 80% of colorectal cancers. Mechanistically its major function as a tumour suppressor is to negatively regulate Wnt signalling, preventing the activation of Wnt target genes. Due to the difficulties of studying intestinal cells ex vivo, a plethora of studies have been performed investigating gene function within the murine intestine following Apc loss. In this grant we propose to validate the Drosophila fly intestine as a model system to investigate Apc loss. Specifically we aim to use the Drosophila intestine as a screen for Wnt targets that are functionally important for the phenotypes of Apc loss. These experiments could dramatically reduce the numbers of murine intestinal experiments performed and yield new insights in to colorectal carcinogenesis.

Impacts

Publications

  1. Faller WJ et al. (2015). mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 517(7535):497-500. doi: 10.1038/nature13896
  2. Cordero JB et al. (2014). c-Src drives intestinal regeneration and transformation. EMBO J 33(13):1474-91. doi: 10.1002/embj.201387454
  3. Lourenço FC et al. (2014). Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation. Gut 63(3):480-93. doi: 10.1136/gutjnl-2012-303883
  4. Myant KB et al. (2013). ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell 12(6):761-73. doi: 10.1016/j.stem.2013.04.006
  5. Cordero JB and Sansom OJ (2012). Wnt signalling and its role in stem cell-driven intestinal regeneration and hyperplasia. Acta Physiologica 204(1):137-43. doi: 10.1111/j.1748-1716.2011.02288.x
  6. Cordero JB et al. (2012). Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila. The EMBO Journal 31(19):3901-3917. doi: 10.1038/emboj.2012.248
  7. Cordero JB et al. (2012). Non-autonomous crosstalk between the Jak/Stat and Egfr pathways mediates Apc1-driven intestinal stem cell hyperplasia in the Drosophila adult midgut. Development 139(24):4524-35. doi: 10.1242/dev.078261