Published September 7, 2018 | Version v1
Journal article Restricted

Rewiring urea cycle metabolism in cancer to support anabolism

  • 1. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
  • 2. Center for Molecular Oncology, Barts Cancer Institute
  • 3. CIC bioGUNE, Derio, Spain; CIBERONC, Madrid, Spain

Description

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.

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Funding

NO-BRAINER – Developing therapies for Nitric Oxide (NO) related neurodegeneration 618113
European Commission
NO-DISEASE – Developing novel therapies for systemic disorders by regulating Nitric Oxide (NO) substrates' availability 614204
European Commission
CANCERMETAB – Metabolic requirements for prostate cancer cell fitness 336343
European Commission
MetaboMARKER – A metabolism-based prognostic biomarker for prostate cancer 754627
European Commission