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hScrib is a functional homologue of the Drosophila tumour suppressor Scribble

Oncogene volume 22, pages 9225–9230 (2003)Cite this article

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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References

  • Behrens J, Birchmeier W, Goodman SL and Imhof BA . (1985). J. Cell Biol., 101, 1307–1315.

  • Bilder D, Li M and Perrimon N . (2000). Science, 289, 113–116.

  • Bilder D and Perrimon N . (2000). Nature, 403, 676–680.

  • Bissell MJ and Radisky D . (2001). Nat. Rev. Cancer, 1, 46–54.

  • Boussioutas A, Li H, Liu J, Waring P, Lade S, Holloway AJ, Taupin D, Gorringe K, Haviv I, Desmond PV and Bowtell DD . (2003). Cancer Res., 63, 2569–2577.

  • Brand AH and Perrimon N . (1993). Development, 118, 401–415.

  • Gateff E . (1994). Int. J. Dev. Biol., 38, 565–590.

  • Huang JH, Rajkovic A, Szafranski P, Ochsner S, Richards J and Goode S . (2003). Gene Expression Patterns, 3, 3–11.

  • Humbert P, Russell S and Richardson H . (2003). Bioessays, 25, 542–553.

  • Ishidate T, Matsumine A, Toyoshima K and Akiyama T . (2000). Oncogene, 19, 365–372.

  • Lee T and Luo L . (1999). Neuron, 22, 451–461.

  • Liu LX, Liu ZH, Jiang HC, Qu X, Zhang WH, Wu LF, Zhu AL, Wang XQ and Wu M . (2002). World J. Gastroenterol., 8, 580–585.

  • Ludford-Menting MJ, Thomas SJ, Crimeen B, Harris LJ, Loveland BE, Bills M, Ellis S and Russell SM . (2002). J. Biol. Chem., 277, 4477–4484.

  • Makino K, Kuwahara H, Masuko N, Nishiyama Y, Morisaki T, Sasaki J, Nakao M, Kuwano A, Nakata M, Ushio Y and Saya H . (1997). Oncogene, 14, 2425–2433.

  • Mantovani F and Banks L . (2001). Oncogene, 20, 7874–7887.

  • Mathew D, Gramates LS, Packard M, Thomas U, Bilder D, Perrimon N, Gorczyca M and Budnik V . (2002). Curr. Biol., 12, 531–539.

  • Montcouquiol M, Rachel RA, Lanford PJ, Copeland NG, Jenkins NA and Kelley MW . (2003). Nature, 423, 173–177.

  • Murdoch JN, Henderson DJ, Doudney K, Gaston-Massuet C, Phillips HM, Paternotte C, Arkell R, Stanier P and Copp AJ . (2003). Hum. Mol. Genet., 12, 87–98.

  • Nakagawa S and Huibregtse JM . (2000). Mol. Cell. Biol., 20, 8244–8253.

  • Stevenson BR, Siliciano JD, Mooseker MS and Goodenough DA . (1986). J. Cell Biol., 103, 755–766.

  • Thiery JP . (2002). Nat. Rev. Cancer, 2, 442–454.

  • Thomas U, Phannavong B, Muller B, Garner CC and Gundelfinger ED . (1997). Mech. Dev., 62, 161–174.

  • Woodhouse E, Hersperger E and Shearn A . (1998). Dev. Genes Evol., 207, 542–550.

  • Woods DF and Bryant PJ . (1991). Cell, 66, 451–464.

  • Woods DF, Hough C, Peel D, Callaini G and Bryant PJ . (1996). J. Cell Biol., 134, 1469–1482.

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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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Authors and Affiliations

  1. Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria, 3002, Australia

    Lukas E Dow, Rosa Muratore & Patrick O Humbert

  2. Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, 3005, Australia

    Lukas E Dow

  3. Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria, 3002, Australia

    Anthony M Brumby, Michelle L Coombe & Helena E Richardson

  4. Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria, 3002, Australia

    Karin A Sedelies & Joseph A Trapani

  5. Department of Pathology, University of Melbourne, Parkville, Victoria, 3005, Australia

    Joseph A Trapani, Sarah M Russell & Patrick O Humbert

  6. Immune Signaling Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria, 3002, Australia

    Sarah M Russell

  7. Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, 3005, Australia

    Helena E Richardson

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  1. Lukas E Dow
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  2. Anthony M Brumby
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Correspondence to Patrick O Humbert.

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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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