Systemic muscle wasting and coordinated tumour response drive tumourigenesis.

Holly Newton, Yi-Fang Wang, Laura Camplese, Joao B Mokochinski, Holger B Kramer, André E X Brown, Louise Fets, Susumu Hirabayashi

Nature communications 2020 Sep 16

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Cancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic perturbations remain incompletely understood. Here, we use a Drosophila model of high-sugar diet (HSD)-enhanced tumourigenesis to uncover a systemic host-tumour metabolic circuit that supports tumour growth. We demonstrate coordinate induction of systemic muscle wasting with tumour-autonomous Yorkie-mediated SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Insights from this whole-animal Drosophila model provide a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of a perturbed systemic metabolic network.

Citation

Holly Newton, Yi-Fang Wang, Laura Camplese, Joao B Mokochinski, Holger B Kramer, André E X Brown, Louise Fets, Susumu Hirabayashi. Systemic muscle wasting and coordinated tumour response drive tumourigenesis. Nature communications. 2020 Sep 16;11(1):4653