Suppression of MTHFD2 in MCF-7 Breast Cancer Cells Increases Glycolysis, Dependency on Exogenous Glycine, and Sensitivity to Folate Depletion
File(s)
Author(s)
Type
Journal Article
Abstract
Methylenetetrahydrofolate dehydrogenase (NAD(P)+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) is a mitochondrial enzyme involved in folate metabolism. A number of recent studies have highlighted this enzyme as being highly expressed in many solid tumors, including breast cancer, and to be correlated with poor survival. However, the metabolic functions of MTHFD2 in cancer cells have not been well-defined. To investigate the function of MTHFD2 in breast cancer cells, we generated and characterized MCF-7 cells with stable suppression of MTHFD2 expression using a combination of cellular assays and metabolic profiling. Loss of MTHFD2 caused MCF7 cells to become glycine auxotrophs, that is, reliant on exogenous glycine, and more sensitive to exogenous folate depletion. Another prominent metabolic alteration observed as a consequence of MTHFD2 suppression was a more glycolytic phenotype, consistent with widespread modifications of cellular metabolism. Collectively, these data suggest that targeting MTHFD2 activity is likely to influence multiple metabolic pathways in breast cancer and could be combined with a range of antimetabolite therapies.
Date Issued
2016-06-17
Date Acceptance
2016-06-01
Citation
Journal of Proteome Research, 2016, 15 (8), pp.2618-2625
ISSN
1535-3907
Publisher
American Chemical Society
Start Page
2618
End Page
2625
Journal / Book Title
Journal of Proteome Research
Volume
15
Issue
8
Copyright Statement
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, © 2016 American Chemical Society, after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.jproteome.6b00188.
Subjects
MCF-7
MTHFD2
cancer
folate
glycine
glycolysis
metabolomics
shRNA
Biochemistry & Molecular Biology
06 Biological Sciences
03 Chemical Sciences
Publication Status
Published