Loss of apical-basal polarity is an early event in the development of epithelial cancers. Epithelial cell polarity is maintained by three highly conserved polarity complexes, Par, Crumbs (CRB) and Scribble (SCRIB). The Scribble polarity complex (or module) is comprised of proteins encoded by 3 or 4 genes: SCRIB (Dmel\scrib), DLG1 (Dmel\dlg1) and LLGL1 or LLGL2 (Dmel\l(2)gl). Each of the corresponding Drosophila genes has been used in models of epithelial cancer (FBhh0000587, FBhh0000591, FBhh0000678). The human genes Hsap\SCRIB and Hsap\LLGL1 have introduced into flies; both exhibit partial heterologous rescue (functional complementation) of mutant phenotypes of the corresponding fly gene.
Much of the work in Drosophila modeling epithelial cancer uses a loss-of-function alleles of one of the Scribble polarity complex genes in combination with a Ras85D activated mutation; see 'cancer, epithelial, RAS-SCRIB-related' (FBhh0000585), 'cancer, epithelial, RAS-LLGL-related' (FBhh0000588), and 'cancer, epithelial, RAS-DLG1-related' (FBhh0000589). Other combinations characterized in flies include 'cancer, epithelial, LLGL-YAP1-related' (FBhh0000590) and 'cancer, epithelial, NOTCH-SCRIB-related' (FBhh0000679).
Experiments characterizing the role of the Scribble complex genes in flies typically assay phenotypes in the larval wing imaginal disc, a simple, two-layered, proliferating epithelium with an intact basement membrane. When function of the Scribble polarity complex is lost in epithelial cells, the cells round up and become multilayered. In imaginal discs during the larval stage, mutant tissue proliferates to more than five times the wild-type cell number and eventually kills the animal.
[updated May 2018 by FlyBase; FBrf0222196]
Loss of cell polarity is a hallmark for carcinoma (Khursheed and Bashyam, 2014; pubmed:24499799).