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Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer

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 enzym...

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Autores principales: Nilsson, Roland, Jain, Mohit, Madhusudhan, Nikhil, Sheppard, Nina Gustafsson, Strittmatter, Laura, Kampf, Caroline, Huang, Jenny, Asplund, Anna, Mootha, Vamsi K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106362/
https://www.ncbi.nlm.nih.gov/pubmed/24451681
http://dx.doi.org/10.1038/ncomms4128
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author Nilsson, Roland
Jain, Mohit
Madhusudhan, Nikhil
Sheppard, Nina Gustafsson
Strittmatter, Laura
Kampf, Caroline
Huang, Jenny
Asplund, Anna
Mootha, Vamsi K
author_facet Nilsson, Roland
Jain, Mohit
Madhusudhan, Nikhil
Sheppard, Nina Gustafsson
Strittmatter, Laura
Kampf, Caroline
Huang, Jenny
Asplund, Anna
Mootha, Vamsi K
author_sort Nilsson, Roland
collection PubMed
description 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.
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spelling pubmed-41063622014-07-22 Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer Nilsson, Roland Jain, Mohit Madhusudhan, Nikhil Sheppard, Nina Gustafsson Strittmatter, Laura Kampf, Caroline Huang, Jenny Asplund, Anna Mootha, Vamsi K Nat Commun Article 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. 2014 /pmc/articles/PMC4106362/ /pubmed/24451681 http://dx.doi.org/10.1038/ncomms4128 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Nilsson, Roland
Jain, Mohit
Madhusudhan, Nikhil
Sheppard, Nina Gustafsson
Strittmatter, Laura
Kampf, Caroline
Huang, Jenny
Asplund, Anna
Mootha, Vamsi K
Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
title Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
title_full Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
title_fullStr Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
title_full_unstemmed Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
title_short Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer
title_sort metabolic enzyme expression highlights a key role for mthfd2 and the mitochondrial folate pathway in cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106362/
https://www.ncbi.nlm.nih.gov/pubmed/24451681
http://dx.doi.org/10.1038/ncomms4128
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