Transformed Drosophila cells evade diet-mediated insulin resistance through wingless signaling.
Cell
; 154(3): 664-75, 2013 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-23911328
ABSTRACT
The risk of specific cancers increases in patients with metabolic dysfunction, including obesity and diabetes. Here, we use Drosophila as a model to explore the effects of diet on tumor progression. Feeding Drosophila a diet high in carbohydrates was previously demonstrated to direct metabolic dysfunction, including hyperglycemia, hyperinsulinemia, and insulin resistance. We demonstrate that high dietary sugar also converts Ras/Src-transformed tissue from localized growths to aggressive tumors with emergent metastases. Whereas most tissues displayed insulin resistance, Ras/Src tumors retained insulin pathway sensitivity, increased the ability to import glucose, and resisted apoptosis. High dietary sugar increased canonical Wingless/Wnt pathway activity, which upregulated insulin receptor gene expression to promote insulin sensitivity. The result is a feed-forward circuit that amplified diet-mediated malignant phenotypes within Ras/Src-transformed tumors. By targeting multiple steps in this circuit with rationally applied drug combinations, we demonstrate the potential of combinatorial drug intervention to treat diet-enhanced malignant tumors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Carboidratos da Dieta
/
Transdução de Sinais
/
Proteínas de Drosophila
/
Modelos Animais de Doenças
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Drosophila
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Proteína Wnt1
/
Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos