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 and Susumu Hirabayashi ()
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Holly Newton: Medical Research Council London Institute of Medical Sciences
Yi-Fang Wang: Medical Research Council London Institute of Medical Sciences
Laura Camplese: Medical Research Council London Institute of Medical Sciences
Joao B. Mokochinski: Medical Research Council London Institute of Medical Sciences
Holger B. Kramer: Medical Research Council London Institute of Medical Sciences
André E. X. Brown: Medical Research Council London Institute of Medical Sciences
Louise Fets: Medical Research Council London Institute of Medical Sciences
Susumu Hirabayashi: Medical Research Council London Institute of Medical Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-18502-9

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