Systemic muscle wasting and coordinated tumour response drive tumourigenesis

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-t...

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Autores principales: Newton, Holly, Wang, Yi-Fang, Camplese, Laura, Mokochinski, Joao B., Kramer, Holger B., Brown, André E. X., Fets, Louise, Hirabayashi, Susumu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495438/
https://www.ncbi.nlm.nih.gov/pubmed/32938923
http://dx.doi.org/10.1038/s41467-020-18502-9
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author Newton, Holly
Wang, Yi-Fang
Camplese, Laura
Mokochinski, Joao B.
Kramer, Holger B.
Brown, André E. X.
Fets, Louise
Hirabayashi, Susumu
author_facet Newton, Holly
Wang, Yi-Fang
Camplese, Laura
Mokochinski, Joao B.
Kramer, Holger B.
Brown, André E. X.
Fets, Louise
Hirabayashi, Susumu
author_sort Newton, Holly
collection PubMed
description 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.
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spelling pubmed-74954382020-10-01 Systemic muscle wasting and coordinated tumour response drive tumourigenesis Newton, Holly Wang, Yi-Fang Camplese, Laura Mokochinski, Joao B. Kramer, Holger B. Brown, André E. X. Fets, Louise Hirabayashi, Susumu Nat Commun Article 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. Nature Publishing Group UK 2020-09-16 /pmc/articles/PMC7495438/ /pubmed/32938923 http://dx.doi.org/10.1038/s41467-020-18502-9 Text en © Crown 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Newton, Holly
Wang, Yi-Fang
Camplese, Laura
Mokochinski, Joao B.
Kramer, Holger B.
Brown, André E. X.
Fets, Louise
Hirabayashi, Susumu
Systemic muscle wasting and coordinated tumour response drive tumourigenesis
title Systemic muscle wasting and coordinated tumour response drive tumourigenesis
title_full Systemic muscle wasting and coordinated tumour response drive tumourigenesis
title_fullStr Systemic muscle wasting and coordinated tumour response drive tumourigenesis
title_full_unstemmed Systemic muscle wasting and coordinated tumour response drive tumourigenesis
title_short Systemic muscle wasting and coordinated tumour response drive tumourigenesis
title_sort systemic muscle wasting and coordinated tumour response drive tumourigenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495438/
https://www.ncbi.nlm.nih.gov/pubmed/32938923
http://dx.doi.org/10.1038/s41467-020-18502-9
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