uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
Show others and affiliations
2014 (English)In: Nature Communications, ISSN 2041-1723, Vol. 5, 3128- p.Article in journal (Refereed) Published
Abstract [en]

Metabolic remodeling is now widely regarded as a hallmark of cancer, but it is not clear whether individual metabolic strategies are frequently exploited by many tumours. Here we compare messenger RNA profiles of 1,454 metabolic enzymes across 1,981 tumours spanning 19 cancer types to identify enzymes that are consistently differentially expressed. Our meta-analysis recovers established targets of some of the most widely used chemotherapeutics, including dihydrofolate reductase, thymidylate synthase and ribonucleotide reductase, while also spotlighting new enzymes, such as the mitochondrial proline biosynthetic enzyme PYCR1. The highest scoring pathway is mitochondrial one-carbon metabolism and is centred on MTHFD2. MTHFD2 RNA and protein are markedly elevated in many cancers and correlated with poor survival in breast cancer. MTHFD2 is expressed in the developing embryo, but is absent in most healthy adult tissues, even those that are proliferating. Our study highlights the importance of mitochondrial compartmentalization of one-carbon metabolism in cancer and raises important therapeutic hypotheses.

Place, publisher, year, edition, pages
2014. Vol. 5, 3128- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-220933DOI: 10.1038/ncomms4128ISI: 000331084400037OAI: oai:DiVA.org:uu-220933DiVA: diva2:707389
Available from: 2014-03-24 Created: 2014-03-24 Last updated: 2014-03-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Kampf, CarolineAsplund, Anna
By organisation
Molecular and Morphological Pathology
In the same journal
Nature Communications
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 196 hits
ReferencesLink to record
Permanent link

Direct link