Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Open accessAbstract
More Glycine, Please: To better characterize metabolic properties of cancer cells, Jain et al. (p. 1040 ; see the Perspective by Tomita and Kami ) measured systematically the concentrations of hundreds of metabolites in cell culture medium in which 60 different cancer cell lines were growing. The fastest growing cancer cells tended to consume glycine, whereas more slowly growing cells excreted some glycine. The rapidly growing cancer cells appeared to need glycine for synthesis of purine nucleotides required for continued synthesis of DNA. Interfering with glycine metabolism slowed growth of the rapidly proliferating cancer cells. Thus, an increased dependence on glycine by rapidly growing cancer cells could potentially provide a target for therapeutic intervention.
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Certain tumors are dependent on uptake of environmental serine.
“Certain tumors are dependent on uptake of environmental serine (Jain et al., 2012; Maddocks et al., 2013; Maddocks et al., 2017), and limiting plasma serine availability can be beneficial for patients with these cancers.”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Jain et al., 2012
Cancer cells proliferating in vitro consume glutamine far in excess of any other amino acid and are often dependent on extracellular glutamine for survival.
“Glutamine is a non-essential amino acid, and yet cancer cells proliferating in vitro consume glutamine far in excess of any other amino acid and are often dependent on extracellular glutamine for survival (DeBerardinis and Cheng, 2010; Eagle, 1955; Jain et al., 2012).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Jain et al., 2012
Across the NCI-60 panel of cell lines, SHMT2 expression had a stronger correlation with proliferation rate than SHMT1.
“Across the NCI-60 panel of cell lines, SHMT2 expression held a stronger correlation with proliferation rate than that of SHMT1.”
From A review of small-molecule inhibitors of one-carbon enzymes: SHMT2 and MTHFD2 in the spotlight (2021) · cites this paper as [8]
The mitochondrial isoforms of SHMT and MTHFD, SHMT2 and MTHFD2, are clinically relevant in the context of cancer.
“Literature continues to suggest that the mitochondrial isoforms of these enzymes are clinically relevant in the context of cancer.”
From A review of small-molecule inhibitors of one-carbon enzymes: SHMT2 and MTHFD2 in the spotlight (2021) · cites this paper as [8]
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References 43 · Cited by 1,403
- Authors
- Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K.
- Affiliations
- Broad Institute (US)
- La Jolla Institute for Immunology (US)
- Harvard University (US)
- Corresponding author
- Jain, Mohit
- Nilsson, Roland
- Mootha, Vamsi K.
- ORCID
- Venue
- Science
- Published
- 2012-05-25
- Volume
- 336
- Issue
- 6084
- Pages
- 1040-1044
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3526189
- OpenAlex
- W2108195113
- Cited by
- 1,403
- References
- 43
- Citations by year
- 2026: 50 · 2025: 90 · 2024: 92 · 2023: 80 · 2022: 108 · 2021: 127 · 2020: 97 · 2019: 117 · 2018: 117 · 2017: 105 · 2016: 128 · 2015: 93 · 2014: 94 · 2013: 77 · 2012: 27
- FWCI
- 30.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K08HL107451)
- National Institute of General Medical Sciences (R01GM026875)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK081457)
- National Institute of Environmental Health Sciences (R01ES027595)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- glycine, tumor cell proliferation, metabolic reprogramming, metabolite profiling, NCI-60 cell lines, metabolic vulnerability, breast cancer mortality, cancer metabolism
- MeSH terms
- Breast Neoplasms, Cell Cycle, Cell Line, Cell Transformation, Neoplastic, Chromatography, Liquid, Culture Media, Glycine, Humans, Mitochondria, Neoplasms, Purines, Gene Expression, Gene Expression Profiling, Cell Line, Tumor, Cell Proliferation, Tandem Mass Spectrometry, Metabolic Networks and Pathways, Metabolome
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