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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783582922512531456 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7495438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT newtonholly systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis AT wangyifang systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis AT campleselaura systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis AT mokochinskijoaob systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis AT kramerholgerb systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis AT brownandreex systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis AT fetslouise systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis AT hirabayashisusumu systemicmusclewastingandcoordinatedtumourresponsedrivetumourigenesis |