View Program - 63rd Annual Drosophila Research Conference

Cancer patients display multiple metabolic disorders induced by humoral factors secreted by the growing cancerous mass. Collectively termed as paraneoplastic syndromes, these systemic metabolic disorders often contribute to morbidity and even mortality of the patients: anorexia and cachexia being some of the cited examples. The onset of such paraneoplastic syndromes is marked by poor prognosis and often represents end-stage cancer. In certain cancers with the highest mortality rate, new-onset diabetes has been reported as another paraneoplastic phenomenon. Thus, management of cancer-induced diabetes remains a potential route to alleviate morbidity of cancer patients, improve their prognosis and, in certain instances, facilitate their early diagnosis and management. Here we show the systemic fallouts of oncogenic Ras signaling underlies cancer-linked diabetes in Drosophila. We found that a localized Ras activation in a non-vital organ decreases the adult eclosion rate. Further, oncogenic Ras signaling systemically perturbs host metabolism, particularly insulin signaling, with the accompanying onset of obesity, dyslipidemia, hyperglycemia, and, finally, insulin resistance and diabetes. Our results further reveal putative candidate secreted factors from the oncogenic Ras signaling cells as an inducer of these paraneoplastic syndromes. Our findings, therefore, reveal for the first time a causal underpinning of cancer-linked diabetes and the prospect of using Drosophila model for the exploration of therapeutic interventions.

Modeling Paraneoplastic Diabetes in Drosophila