Abstract
Scribble (scrib), discs large (dlg) and lethal giant larvae (lgl) encode proteins that regulate cell polarity and have been identified as neoplastic tumour suppressor genes in Drosophila melanogaster. Here, we have used the Drosophila model system to provide the first functional evidence that human Scribble (hScrib) can act as a tumour suppressor. We show that hScrib protein displays highly polarized localization in mammalian epithelial cells and colocalizes with mammalian Dlg, similar to D. melanogaster Scribble (DmScrib) distribution in Drosophila epithelium. Furthermore, hScrib can rescue the polarity and tumorous overgrowth defects of scrib mutant Drosophila. hScrib therefore can act as an effective tumour suppressor in vivo, regulating both apical–basal polarity and cellular proliferation in a manner similar to that of DmScrib in Drosophila. These data demonstrate that hScrib is a functional homologue of DmScrib and therefore predict an important role for hScrib in the suppression of mammalian tumorigenesis.
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Acknowledgements
We thank G Poortinga for discussions and for comments on the manuscript. We thank the Kazuza DNA Research Institute for the KIAA0147 cDNA clone, D Bilder for the scrib1 fly stock and J Treisman for the ey-FLP; GAL4,FRT82B,GAL80 stock. LED was supported by a Cancer Council Victoria Postgraduate Cancer Research Scholarship. JAT is a Principal Research Fellow of the National Health & Medical Research Council of Australia, SMR and HER are Wellcome Senior Research Fellows in Medical Science and POH is a Special Fellow of the Leukemia and Lymphoma Society of America.
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Dow, L., Brumby, A., Muratore, R. et al. hScrib is a functional homologue of the Drosophila tumour suppressor Scribble. Oncogene 22, 9225–9230 (2003). https://doi.org/10.1038/sj.onc.1207154
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DOI: https://doi.org/10.1038/sj.onc.1207154
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