title: Nutrient restriction enhances the proliferative potential of cells lacking the tumor suppressor PTEN in mitotic tissues.
abstract: How single cells in a mitotic tissue progressively acquire hallmarks of cancer is poorly understood. We exploited mitotic recombination in developing Drosophila imaginal tissues to analyze the behavior of cells devoid of the tumor suppressor PTEN, a negative regulator of PI3K signaling, under varying nutritional conditions. Cells lacking PTEN strongly overproliferated specifically in nutrient restricted larvae. Although the PTEN mutant cells were sensitive to starvation, they successfully competed with neighboring cells by autonomous and non-autonomous mechanisms distinct from cell competition. The overgrowth was strictly dependent on the activity of the downstream components Akt/PKB and TORC1, and a reduction in amino acid uptake by reducing the levels of the amino acid transporter Slimfast caused clones of PTEN mutant cells to collapse. Our findings demonstrate how limiting nutritional conditions impact on cells lacking the tumor suppressor PTEN to cause hyperplastic overgrowth. DOI:http://dx.doi.org/10.7554/eLife.00380.001.
authors.affiliation: Institute of Molecular Systems Biology , ETH Zürich , Zürich , Switzerland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nowak
authors.forename: Gerhard
authors.initials: G
authors.lastname: Seisenbacher
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker
mesh_terms: D000222:Adaptation, Physiological; D026905:Amino Acid Transport Systems / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D049109:Cell Proliferation; D004330:Drosophila / Q000196:embryology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D007328:Insulin / Q000378:metabolism; D007814:Larva / Q000201:enzymology; D008938:Mitosis; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015002:Yeast, Dried / Q000378:metabolism
chemical_list: D026905:Amino Acid Transport Systems; D029721:Drosophila Proteins; D007328:Insulin; D018129:Phosphatidylinositol Phosphates; C570998:TORC1 protein complex, Drosophila; D014157:Transcription Factors; C478492:slif protein, Drosophila; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487101:PTEN protein, Drosophila
keywords: D. melanogaster; PTEN; apoptosis; hyperplasia; insulin signaling; nutrient restriction; tumor suppression