TY - JOUR T1 - Systemic muscle wasting and coordinated tumour response drive tumourigenesis JF - bioRxiv DO - 10.1101/785022 SP - 785022 AU - Holly Newton AU - Yi-Fang Wang AU - Laura Camplese AU - André E.X. Brown AU - Susumu Hirabayashi Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/09/27/785022.abstract N2 - Cancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic pertubations remain incompletely understood. Here we use a Drosophila model of obesity-enhanced tumourigenesis to uncover a systemic host-tumour nutrient circuit that supports tumour growth. We demonstrate coordinate induction of systemic cachexia-like muscle wasting with tumour-autonomous SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. This coordinated induction of cachexia and SLC36-transporters pertains to human kidney cancer and associates with significantly worse survival outcomes. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Combining insights from whole-animal Drosophila models and human cancer database analysis provides a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of perturbed systemic metabolic network. ER -