Cancer cells demand excessive nutrients to support their proliferation but how cancer
cells sense and promote growth in the nutrient favorable conditions remain incompletely
understood. Epidemiological studies have indicated that obesity is a risk factor for various types of
cancers. Feeding Drosophila a high dietary sugar was previously demonstrated to not only direct
metabolic defects including obesity and organismal insulin resistance, but also transform Ras/Srcactivated
cells into aggressive tumors. Here we demonstrate that Ras/Src-activated cells are
sensitive to perturbations in the Hippo signaling pathway. We provide evidence that nutritional cues
activate Salt-inducible kinase, leading to Hippo pathway downregulation in Ras/Src-activated cells.
The result is Yorkie-dependent increase in Wingless signaling, a key mediator that promotes
diet-enhanced Ras/Src-tumorigenesis in an otherwise insulin-resistant environment. Through this
mechanism, Ras/Src-activated cells are positioned to efficiently respond to nutritional signals and
ensure tumor growth upon nutrient rich condition including obesity.