DOI: 10.1126/science.289.5476.113. Cooperative Regulation of Cell Polarity and Growth by <i>Drosophila</i> Tumor Suppressors

Cooperative Regulation of Cell Polarity and Growth by Drosophila Tumor Suppressors

10.1126/science.289.5476.113

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

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.

Bibliography

Bilder, D., Li, M., & Perrimon, N. (2000). Cooperative Regulation of Cell Polarity and Growth by Drosophila Tumor Suppressors. Science, 289(5476), 113â116.

Authors 3

David Bilder (first)
Min Li (additional)
Norbert Perrimon (additional)

References 33 Referenced 821

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. Alleles used to generate clones were scrib 1− FRT82B scrib 2− FRT82B 4w3-FRT40 lgl 4− FRT40 (31) and dlg m52 -FRT101. Follicle cell clones were generated with hsFLP stocks carrying ubiquitin-GFP (30) recombined onto FRT101 FRT40 and FRT82B chromosomes.
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GenBank number NM−004524
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We thank M. Bender P. Bryant B. Mechler J. K. Roy A. Shearn D. Strand D. Strutt and D. Woods for generously providing materials and B. Mathey-Prevot and A. Chen for comments on the manuscript. D.B is a Fellow of the American Cancer Society.

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:35 a.m.)
Deposited	1 year, 7 months ago (Jan. 13, 2024, 5:40 a.m.)
Indexed	2 days, 2 hours ago (Aug. 31, 2025, 6:08 a.m.)
Issued	25 years, 1 month ago (July 7, 2000)
Published	25 years, 1 month ago (July 7, 2000)
Published Print	25 years, 1 month ago (July 7, 2000)

Funders 0

None

BibTeX

@article{Bilder_2000, title={Cooperative Regulation of Cell Polarity and Growth by Drosophila Tumor Suppressors}, volume={289}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.289.5476.113}, DOI={10.1126/science.289.5476.113}, number={5476}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Bilder, David and Li, Min and Perrimon, Norbert}, year={2000}, month=jul, pages={113–116} }

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  "abstract": "<jats:p>\n            Loss of cell polarity and tissue architecture are characteristics of malignant cancers derived from epithelial tissues. We provide evidence from\n            <jats:italic>Drosophila</jats:italic>\n            that a group of membrane-associated proteins act in concert to regulate both epithelial structure and cell proliferation. Scribble (Scrib) is a cell junction\u2013localized protein required for polarization of embryonic and, as demonstrated here, imaginal disc and follicular epithelia. We show that the tumor suppressors\n            <jats:italic>lethal giant larvae</jats:italic>\n            (\n            <jats:italic>lgl</jats:italic>\n            ) and\n            <jats:italic>discs-large</jats:italic>\n            (\n            <jats:italic>dlg</jats:italic>\n            ) have identical effects on all three epithelia, and that\n            <jats:italic>scrib</jats:italic>\n            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.\n            <jats:italic>scrib</jats:italic>\n            ,\n            <jats:italic>dlg</jats:italic>\n            , and\n            <jats:italic>lgl</jats:italic>\n            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.\n          </jats:p>",
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