2. Academic Validation
  3. Rewiring urea cycle metabolism in cancer to support anabolism

Rewiring urea cycle metabolism in cancer to support anabolism

  • Nat Rev Cancer. 2018 Oct;18(10):634-645. doi: 10.1038/s41568-018-0054-z.
Rom Keshet 1,  Peter Szlosarek 2 3,  Arkaitz Carracedo 4 5 6 7,  Ayelet Erez 8
Affiliations

Affiliations

  • 1 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
  • 2 Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, UK.
  • 3 Barts Health NHS Trust, St Bartholomew's Hospital, London, UK.
  • 4 CIC bioGUNE, Bizkaia, Spain.
  • 5 CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
  • 6 Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
  • 7 Biochemistry and Molecular Biology Department, University of the Basque Country, Bilbao, Spain.
  • 8 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel. [email protected].
PMID: 30194362 DOI: 10.1038/s41568-018-0054-z
Abstract

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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