Cooperative Regulation of Cell Polarity and Growth by Drosophila Tumor Suppressors

American Association for the Advancement of Science (AAAS) - Tập 289 Số 5476 - Trang 113-116 - 2000
David Bilder1, Li Min2, Norbert Perrimon1,2
1Department of Genetics, and
2Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115 USA

Tóm tắt

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.

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