Systemic muscle wasting and coordinated tumour response drive tumourigenesis
Systemic muscle wasting and coordinated tumour response drive tumourigenesis
复制标题
DOI：
10.1038/s41467-020-18502-9
复制
发表时间：
2020-09-16
影响因子：
16.6
通讯作者：
Hirabayashi, Susumu
中科院分区：
文献类型：
--
作者：
Newton, Holly;Wang, Yi-Fang;Hirabayashi, Susumu
癌细胞需要过量的营养物质来支持其增殖，但肿瘤如何在全身代谢紊乱期间利用细胞外氨基酸仍不完全清楚。在这里，我们使用高糖饮食（HSD）增强肿瘤发生的果蝇模型来揭示支持肿瘤生长的系统性宿主-肿瘤代谢回路。我们证明了协调诱导全身肌肉萎缩与肿瘤自主约克介导的SLC 36家族氨基酸转运蛋白表达作为脯氨酸清除程序，以驱动肿瘤发生。我们确定吲哚-3-丙酸作为最佳的氨基酸衍生物，以合理地靶向肿瘤生长的脯氨酸依赖性。从这个全动物果蝇模型的见解提供了一个强大的方法，对识别和治疗利用的氨基酸的脆弱性的肿瘤在一个扰动的全身代谢网络的背景下。癌症是一种与宿主代谢变化相关的全身性疾病。在这里，作者使用果蝇表明，肿瘤利用细胞外脯氨酸响应肌肉萎缩，表明肿瘤诱导肌肉萎缩作为营养清除程序来驱动肿瘤发生。
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. Cancer is a systemic disease that associates with host metabolic changes. Here, the authors show using Drosophila, that tumours exploit extracellular proline in response to muscle wasting, indicating that tumours induce muscle wasting as a nutrient-scavenging programme to drive tumourigenesis.