Dow Lukas E, Brumby Anthony M, Muratore Rosa, Coombe Michelle L, Sedelies Karin A, Trapani Joseph A, Russell Sarah M, Richardson Helena E, Humbert Patrick O
Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria 3002, Australia.
Oncogene. 2003 Dec 18;22(58):9225-30. doi: 10.1038/sj.onc.1207154.
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.
Scribble（scrib）、盘状大蛋白（dlg）和致死性巨幼虫蛋白（lgl）编码调节细胞极性的蛋白质，并且在黑腹果蝇中已被鉴定为肿瘤抑制基因。在此，我们利用果蝇模型系统提供了首个功能性证据，证明人类Scribble（hScrib）可作为肿瘤抑制因子发挥作用。我们发现，hScrib蛋白在哺乳动物上皮细胞中呈现高度极化定位，并与哺乳动物Dlg共定位，类似于黑腹果蝇Scribble（DmScrib）在果蝇上皮中的分布。此外，hScrib能够挽救scrib突变型果蝇的极性和肿瘤过度生长缺陷。因此，hScrib在体内可作为一种有效的肿瘤抑制因子，以类似于果蝇中DmScrib的方式调节顶-基极性和细胞增殖。这些数据表明，hScrib是DmScrib的功能同源物，因此预示hScrib在抑制哺乳动物肿瘤发生中具有重要作用。
