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A Drosophila model linking diet-induced metabolic disease and cancer
Cancer & Metabolism volume 2, Article number: O19 (2014)
Background
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.
Methods
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.
Results
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 [3]. These fly models should provide useful paradigms to study the link between metabolic dysfunction and tumorigenesis in the context of a whole animal.
References
Musselman LP, Fink JL, Narzinski K, Ramachandran PV, Hathiramani SS, Cagan RL, Baranski TJ: A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. Dis Model Mech. 2011, 4: 842-849. 10.1242/dmm.007948.
Na J, Musselman LP, Pendse J, Baranski TJ, Bodmer R, Ocorr K, Cagan R: A Drosophila model of high sugar diet-induced cardiomyopathy. PLoS Genet. 2013, 9: e1003175-10.1371/journal.pgen.1003175.
Hirabayashi S, Baranski TJ, Cagan RL: Transformed Drosophila cells evade diet-mediated insulin resistance through wingless signaling. Cell. 2013, 154: 664-675. 10.1016/j.cell.2013.06.030.
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Hirabayashi, S., Baranski, T. & Cagan, R. A Drosophila model linking diet-induced metabolic disease and cancer. Cancer Metab 2 (Suppl 1), O19 (2014). https://doi.org/10.1186/2049-3002-2-S1-O19
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DOI: https://doi.org/10.1186/2049-3002-2-S1-O19
Keywords
- Obesity
- Insulin Resistance
- Metabolic Disease
- Hyperglycemia
- Insulin Level