Volume 2 Supplement 1
A Drosophila model linking diet-induced metabolic disease and cancer
© Hirabayashi et al; licensee BioMed Central Ltd. 2014
Published: 28 May 2014
Epidemiological studies have provided strong evidence for the association between cancer and metabolic diseases including obesity and diabetes, but the underlying mechanism remains poorly understood.
Feeding Drosophila a diet high in sucrose was previously demonstrated to direct important aspects of type 2 diabetes including insulin-resistance, hyperglycemia, increased insulin levels, accumulation of fat, and heart dysfunction [1, 2]. We used this model to explore the effects of high dietary sucrose on tumor progression of Ras/Src co-activated Drosophila tumor model.
We demonstrate that high dietary sucrose, but not high dietary fat transforms Ras/Src-activated cells from localized growths to aggressive tumors with emergent metastases. Surprisingly, while most tissues displayed aspects of metabolic dysfunction including insulin resistance, Ras/Src-activated tumors retained insulin pathway sensitivity and exhibited an increased ability to import glucose. We provide evidence that this reflects increased insulin signaling, which in turn acts through Wingless/Wnt signaling to promote diet-mediated malignant phenotypes within Ras/Src-activated tumors . These fly models should provide useful paradigms to study the link between metabolic dysfunction and tumorigenesis in the context of a whole animal.
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