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Systemic muscle wasting and coordinated tumour response drive tumourigenesis.


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.

SUBMITTER: Newton H 

PROVIDER: S-EPMC7495438 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Systemic muscle wasting and coordinated tumour response drive tumourigenesis.

Newton Holly H   Wang Yi-Fang YF   Camplese Laura L   Mokochinski Joao B JB   Kramer Holger B HB   Brown André E X AEX   Fets Louise L   Hirabayashi Susumu S  

Nature communications 20200916 1


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 expressio  ...[more]

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