Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors.
Loss of cell polarity and tissue architecture are characteristics of malignant cancers derived from epithelial tissues. We provide evidence from Drosophila that a group of membrane-associated proteins act in concert to regulate both epithelial structure and cell proliferation. Scribble (Scrib) is a cell junction-localized protein required for polarization of embryonic and, as demonstrated here, imaginal disc and follicular epithelia. We show that the tumor suppressors lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all three epithelia, and that scrib also acts as a tumor suppressor. Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. scrib, dlg, and lgl show strong genetic interactions. Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control.
Bilder
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Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. bilder@rascal.med.harvard.edu
Li
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Perrimon
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D000818:Animals; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D002471:Cell Transformation, Neoplastic; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology; D004817:Epidermis / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D017344:Genes, Insect; D016147:Genes, Tumor Suppressor; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D009154:Mutation; D010641:Phenotype; D025521:Tumor Suppressor Proteins
D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; C404683:Scrib protein, Drosophila; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; C070350:dlg1 protein, Drosophila