Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia
Cell Reports, Volume 3, No. 5, Year 2013
Notification
URL copied to clipboard!
Description
The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH), predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target. © 2013 The Authors.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3675675/bin/mmc1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC3675675/bin/mmc2.pdf
Authors & Co-Authors
Adam, Julie
United Kingdom, Oxford
Nuffield Department of Medicine
Yang, Ming
United Kingdom, Oxford
Nuffield Department of Medicine
Bauerschmidt, Christina
United Kingdom, Oxford
Nuffield Department of Medicine
Kitagawa, Mitsuhiro
Japan, Tokyo
Keio University
O'Flaherty, Linda
United Kingdom, Oxford
Nuffield Department of Medicine
Maheswaran, Pratheesh
United Kingdom, Oxford
Nuffield Department of Medicine
Özkan, Gizem
United Kingdom, Oxford
Nuffield Department of Medicine
Sahgal, Natasha
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Baban, Dilair F.A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Kato, Keiko
Japan, Tokyo
Keio University
Saito, Kaori
Japan, Tokyo
Keio University
Iino, Keiko
Japan, Tokyo
Keio University
Igarashi, Kaori
Japan, Tokyo
Keio University
Stratford, M.
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Pugh, Christopher
United Kingdom, Oxford
Nuffield Department of Medicine
Tennant, D. A.
United Kingdom, Birmingham
University of Birmingham
Ludwig, Christian
United Kingdom, Birmingham
University of Birmingham
Davies, Benjamin
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Ratcliffe, Peter J.
United Kingdom, Oxford
Nuffield Department of Medicine
El-Bahrawy, Mona A.
United Kingdom, London
Hammersmith Hospital
Egypt, Alexandria
Faculty of Medicine
Ashrafian, Houman
United Kingdom, Oxford
University of Oxford
Soga, Tomoyoshi
Japan, Tokyo
Keio University
Pollard, Patrick J.
United Kingdom, Oxford
Nuffield Department of Medicine
Statistics
Citations: 78
Authors: 23
Affiliations: 8
Identifiers
Doi:
10.1016/j.celrep.2013.04.006
e-ISSN:
22111247
Research Areas
Cancer
Noncommunicable Diseases