CoChat
Sign Up
Cited by 227Cancer, Hypoxia, and MetabolismFolate and B Vitamins ResearchCancer, Lipids, and Metabolism

The DOI matches its Crossref record; 166 of the 166 references it cites were found in a registry or an index.

Serine, glycine and one‑carbon metabolism in cancer (Review)

Open access
Pan, Sijing, Fan, Ming, Liu, Zhangnan, Li, Xia, Wang, Huijuan·2020·International Journal of Oncology
DOI 10.3892/ijo.2020.5158PMC PMC7864012
Open this paper in CoChat — free accountOpen PDF

Abstract

Serine/glycine biosynthesis and one‑carbon metabolism are crucial in sustaining cancer cell survival and rapid proliferation, and of high clinical relevance. Excessive activation of serine/glycine biosynthesis drives tumorigenesis and provides a single carbon unit for one‑carbon metabolism. One‑carbon metabolism, which is a complex cyclic metabolic network based on the chemical reaction of folate compounds, provides the necessary proteins, nucleic acids, lipids and other biological macromolecules to support tumor growth. Moreover, one‑carbon metabolism also maintains the redox homeostasis of the tumor microenvironment and provides substrates for the methylation reaction. The present study reviews the role of key enzymes with tumor‑promoting functions and important intermediates that are physiologically relevant to tumorigenesis in serine/glycine/one‑carbon metabolism pathways. The related regulatory mechanisms of action of the key enzymes and important intermediates in tumors are also discussed. It is hoped that investigations into these pathways will provide new translational opportunities for human cancer drug development, dietary interventions, and biomarker identification.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3892/ijo.2020.5158

Cites

166 of 166 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 The Serine-glycine biosynthesis pathway. The glycolysis pathway and glutamine catabolism provide an intermediate metabolite, 3-PG, which is gradually catalyzed into serine by PHGDH, PSAT1 and PSPH. Finally, serine is converted into glycine by SHMT1/2. Yellow ovals represent metabolic enzymes. 3-PG, 3-phosphoglycerate; 3-PHP, 3-phosphate hydroxypyruvate; 3-Pser, 3-phosphoserine; α-KG, α-ketoglutarate; OAA, oxaloacetate; PHGDH, phosphoglycerate dehydrogenase; PSAT, phosphoserine aminotransferase; PSPH, phosphoserine phosphatase; SHMT, serine hydroxymethyltransferase; TCA, tricarboxylic acid.
Figure 1 The Serine-glycine biosynthesis pathway. The glycolysis pathway and glutamine catabolism provide an intermediate metabolite, 3-PG, which is gradually catalyzed into serine by PHGDH, PSAT1 and PSPH. Finally, serine is converted into glycine by SHMT1/2. Yellow ovals represent metabolic enzymes. 3-PG, 3-phosphoglycerate; 3-PHP, 3-phosphate hydroxypyruvate; 3-Pser, 3-phosphoserine; α-KG, α-ketoglutarate; OAA, oxaloacetate; PHGDH, phosphoglycerate dehydrogenase; PSAT, phosphoserine aminotransferase; PSPH, phosphoserine phosphatase; SHMT, serine hydroxymethyltransferase; TCA, tricarboxylic acid.CC BY-NC-ND · PubMed Central
Figure 2 Overview of one-carbon metabolism around the folate cycle, methionine cycle and trans-sulfuration pathway. The folate cycle provides one carbon for the methionine cycle, as well as homocysteine, an intermediate product of the methionine cycle, which can be converted into GSH through the trans-sulfuration pathway. Yellow ovals represent metabolic enzymes. 3-PG, 3-phosphoglycerate; BHMT, betaine homocysteine methyltransferase; CBS, cystathionine β-synthase; CTH, cystathionase; DHFR, dihydrofolate reductase; DMG, dimethylglycine; F-THF, 10-formyltetrahydrofolate; GLDC, glycine dehydrogenase; GSH, glutathione; HMT, histone methyl transferase; MAT, methionine adenosyltransferase; me-THF, 5,10-methylenetetrahydrofolate; mTHF, 5-methyl-tetrahydrofolate; MTHFD, methylenetetrahydrofolate dehydrogenase; MTHFR, methylenetetrahydrofolate reductase; MTR, methionine synthase; SAH, S-adenosyl homocysteine; SAHH, SAH hydrolase; SAM, S-adenosylmethionine; SHMT, serine hydroxymethyltransferase; SSP, serine synthesis pathway; THF, tetrahydrofolate.
Figure 2 Overview of one-carbon metabolism around the folate cycle, methionine cycle and trans-sulfuration pathway. The folate cycle provides one carbon for the methionine cycle, as well as homocysteine, an intermediate product of the methionine cycle, which can be converted into GSH through the trans-sulfuration pathway. Yellow ovals represent metabolic enzymes. 3-PG, 3-phosphoglycerate; BHMT, betaine homocysteine methyltransferase; CBS, cystathionine β-synthase; CTH, cystathionase; DHFR, dihydrofolate reductase; DMG, dimethylglycine; F-THF, 10-formyltetrahydrofolate; GLDC, glycine dehydrogenase; GSH, glutathione; HMT, histone methyl transferase; MAT, methionine adenosyltransferase; me-THF, 5,10-methylenetetrahydrofolate; mTHF, 5-methyl-tetrahydrofolate; MTHFD, methylenetetrahydrofolate dehydrogenase; MTHFR, methylenetetrahydrofolate reductase; MTR, methionine synthase; SAH, S-adenosyl homocysteine; SAHH, SAH hydrolase; SAM, S-adenosylmethionine; SHMT, serine hydroxymethyltransferase; SSP, serine synthesis pathway; THF, tetrahydrofolate.CC BY-NC-ND · PubMed Central
Figure 3 One-carbon metabolism integrates nutrient status and cellular functions with appropriate equilibrium in inputs and outputs. One-carbon metabolism can be viewed as a set of two modular units including the folate cycle and methionine cycle. The different nutrient sources and amino acids (serine, glycine, threonine, choline, betaine, methionine and vitamins) are inputted into the one-carbon metabolism and converted into a wide variety of outputs, such as nucleotide metabolism, redox control and post-translational modification. GSH, glutathione; ROS, reactive oxygen species.
Figure 3 One-carbon metabolism integrates nutrient status and cellular functions with appropriate equilibrium in inputs and outputs. One-carbon metabolism can be viewed as a set of two modular units including the folate cycle and methionine cycle. The different nutrient sources and amino acids (serine, glycine, threonine, choline, betaine, methionine and vitamins) are inputted into the one-carbon metabolism and converted into a wide variety of outputs, such as nucleotide metabolism, redox control and post-translational modification. GSH, glutathione; ROS, reactive oxygen species.CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

2 retracted

Show all 166 references

Cited by

Sorted by citations

See all 227

Related

Metadata

Authors
Pan, S., Fan, M., Liu, Z., Li, X., & Wang, H.
Affiliations
Henan University (CN)
Corresponding author
  • Li, Xia
  • Wang, Huijuan
ORCID
Venue
International Journal of Oncology
Publisher
Spandidos Publications
Published
2020-12-11
Volume
58
Issue
2
Pages
158-170
ISSN
  • 1019-6439 (ISSN-L)
  • 1791-2423
DOI
10.3892/ijo.2020.5158
PMC
PMC7864012
OpenAlex
W3112083241
Cited by
227
References
166
Citations by year
2026: 58 · 2025: 64 · 2024: 37 · 2023: 36 · 2022: 23 · 2021: 9
FWCI
1.73
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • International Journal of Oncology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81872023)
  • China Postdoctoral Science Foundation (2018M642742, 81872023)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
serine biosynthesis, glycine synthesis, one-carbon metabolism, folate metabolism, cancer metabolism, carcinogenesis, DNA methylation, anticancer drug development, dietary intervention, biomarkers
MeSH terms
Warburg Effect, Oncologic, Animals, Antineoplastic Agents, Carbon, Disease Models, Animal, Glycine, Humans, Methylation, Neoplasms, Oxidation-Reduction, Serine, Mice, Metabolic Networks and Pathways, Tumor Microenvironment, Carcinogenesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review