Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis
Open accessAbstract
Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.
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GLDC is a mitochondrial enzyme that catalyzes the first step of glycine catabolism and is hyperactive in various cancers.
“glycine decarboxylase (GLDC), a mitochondrial enzyme that catalyzes the first step of glycine catabolism and is hyperactive in various cancers [70–72].”
From Acetylation: a new target for protein degradation in cancer (2025) · cites this paper as [71]
In “GLDC Is a Metabolic Oncogene” (page not provided), the paper says GLDC catalyzes the irreversible rate-limiting step of glycine catabolism. In “GLDC and Glycine Metabolism Are Relevant to Human Cancer Patients” (page not provided), it reports increased GLDC expression in many cancers. Our copy does not identify GLDC as mitochondrial or establish that its enzymatic activity is elevated across those cancers; increased expression is not the same measurement. (LLM, conf=0.85)
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- Authors
- Zhang, W. C., Shyh-Chang, N., Yang, H., Rai, A., Umashankar, S., Ma, S., Soh, B. S., Sun, L. L., Tai, B. C., Nga, M. E., Bhakoo, K. K., Jayapal, S. R., Nichane, M., Yu, Q., Ahmed, D. A., Tan, C., Sing, W. P., Tam, J., Thirugananam, A., Noghabi, M. S., Huei Pang, Y., Ang, H. S., Mitchell, W., Robson, P., Kaldis, P., Soo, R. A., Swarup, S., Lim, E. H., & Lim, B.
- Affiliations
- Tan Tock Seng Hospital (SG)
- National University of Singapore (SG)
- Genome Institute of Singapore (SG)
- National University Hospital (SG)
- Singapore Bioimaging Consortium (SG)
- Institute of Molecular and Cell Biology (SG)
- Nanyang Technological University (SG)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Lim, Elaine Hsuen
- Lim, Bing
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 148
- Issue
- 1-2
- Pages
- 259-272
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2159588477
- Cited by
- 660
- References
- 46
- Citations by year
- 2026: 13 · 2025: 33 · 2024: 31 · 2023: 43 · 2022: 38 · 2021: 56 · 2020: 44 · 2019: 58 · 2018: 52 · 2017: 50 · 2016: 51 · 2015: 55 · 2014: 61 · 2013: 45 · 2012: 29
- FWCI
- 20.11
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-03-02)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 563 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Agency for Science, Technology and Research
- Biomedical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- glycine decarboxylase, non-small cell lung cancer, cancer stem cells, LIN28B, glycine metabolism, serine metabolism, glycolysis, pyrimidine metabolism, carcinogenesis, tumor cell proliferation, prognostic factors, cancer therapy targets
- MeSH terms
- Amino Acid Sequence, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, DNA-Binding Proteins, Fetal Proteins, Glycine, Humans, Lung Neoplasms, Molecular Sequence Data, Neoplasms, Serine, Transplantation, Heterologous, Antigens, CD, Cell Adhesion Molecules, Neuronal, Sequence Alignment, RNA-Binding Proteins, Thermus thermophilus, Activated-Leukocyte Cell Adhesion Molecule, Cell Line, Tumor, Glycine Dehydrogenase (Decarboxylating)
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