文章：

在癌症中重新布线尿素循环代谢以支持合成代谢

Rewiring urea cycle metabolism in cancer to support anabolism

原文发布日期：2018-09-07

DOI: 10.1038/s41568-018-0054-z

类型: Review Article

开放获取: 否

英文摘要：

Cancer cells reprogramme metabolism to maximize the use of nitrogen and carbon for the anabolic synthesis of macromolecules that are required during tumour proliferation and growth. To achieve this aim, one strategy is to reduce catabolism and nitrogen disposal. The urea cycle (UC) in the liver is the main metabolic pathway to convert excess nitrogen into disposable urea. Outside the liver, UC enzymes are differentially expressed, enabling the use of nitrogen for the synthesis of UC intermediates that are required to accommodate cellular needs. Interestingly, the expression of UC enzymes is altered in cancer, revealing a revolutionary mechanism to maximize nitrogen incorporation into biomass. In this Review, we discuss the metabolic benefits underlying UC deregulation in cancer and the relevance of these alterations for cancer diagnosis and therapy.

摘要翻译： 

多胺代谢及其分子功能的研究进展，以及对其在癌症中变化的认识，促使针对多胺代谢的抗癌策略再度引起关注。对多胺代谢与其他癌症驱动通路（包括PTEN–PI3K–mTOR复合物1、WNT信号传导和RAS通路）之间相互作用日益深入的了解，提示了具有重要临床前景的潜在联合疗法。此外，针对多胺的治疗和预防药物的临床试验数量不断增加，且前景广阔。对多胺分解代谢失调与致癌作用之间联系的分子机制的新见解，提出了可用于高危个体癌症预防的其他策略。另外，多胺阻断疗法——一种同时抑制多胺生物合成和阻断多胺转运的策略——可能比单纯基于多胺耗竭的疗法更有效，并可能涉及抗肿瘤免疫反应。这些发现为利用异常多胺代谢进行抗癌治疗开辟了新的研究途径。

原文链接：

Rewiring urea cycle metabolism in cancer to support anabolism