Systemic muscle wasting and coordinated tumour response drive tumourigenesis
File(s)
Published version
Author(s)
Type
Journal Article
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 Issued
2020-09-16
Date Acceptance
2020-08-13
Citation
Nature Communications, 2020, 11
ISSN
2041-1723
Publisher
Nature Research
Journal / Book Title
Nature Communications
Volume
11
Copyright Statement
© Crown 2020. 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 giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32938923
PII: 10.1038/s41467-020-18502-9
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
AMINO-ACID TRANSPORTERS
INSULIN-RESISTANCE
CANCER CACHEXIA
DROSOPHILA
EXPRESSION
GROWTH
PROTEIN
Amino Acid Transport Systems
Animals
Animals, Genetically Modified
Carcinogenesis
Dietary Sugars
Drosophila Proteins
Drosophila melanogaster
Fibroblast Growth Factors
Gene Expression Profiling
Hemolymph
Larva
Muscle Weakness
Muscle, Skeletal
Muscular Atrophy
Neoplasms, Experimental
Nuclear Proteins
Proline
Receptor Protein-Tyrosine Kinases
Trans-Activators
ras Proteins
Muscle, Skeletal
Hemolymph
Animals
Animals, Genetically Modified
Drosophila melanogaster
Neoplasms, Experimental
Muscle Weakness
Muscular Atrophy
ras Proteins
Receptor Protein-Tyrosine Kinases
Fibroblast Growth Factors
Proline
Amino Acid Transport Systems
Trans-Activators
Drosophila Proteins
Nuclear Proteins
Gene Expression Profiling
Larva
Carcinogenesis
Dietary Sugars
Publication Status
Published
Coverage Spatial
England
Article Number
4653
Date Publish Online
2020-09-16