A Drosophila model linking diet-induced metabolic disease and cancer
Cancer & Metabolism volume 2, Article number: O19 (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.
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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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