Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth
Open accessAbstract
// Jinyun Chen 1 , Franklin Chung 1 , Guizhi Yang 1 , Minying Pu 1 , Hui Gao 1 , Wei Jiang 2 , Hong Yin 2 , Vladimir Capka 2 , Shailaja Kasibhatla 3 , Bryan Laffitte 3 , Savina Jaeger 1 , Raymond Pagliarini 1 , Yaoyu Chen 1 and Wenlai Zhou 1 1 Oncology, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States 2 Analytic Science, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States 3 The Genomics Institute of the Novartis Research Foundation, San Diego, California, United States Correspondence: Yaoyu Chen, email : yaoyu.chen@novartis.com, email: // Wenlai Zhou, email: // Keywords : PHGDH, breast cancer cells, in vivo Received : October 24, 2013 Accepted : November 24, 2013 Published : November 26, 2013 Abstract Cancer cells rely on aerobic glycolysis to maintain cell growth and proliferation via the Warburg effect. Phosphoglycerate dehydrogenase (PHDGH) catalyzes the first step of the serine biosynthetic pathway downstream of glycolysis, which is a metabolic gatekeeper both for macromolecular biosynthesis and serine-dependent DNA synthesis. Here, we report that PHDGH is overexpressed in many ER-negative human breast cancer cell lines. PHGDH knockdown in these cells leads to a reduction of serine synthesis and impairment of cancer cell proliferation. However, PHGDH knockdown does not affect tumor maintenance and growth in established breast cancer xenograft models, suggesting that PHGDH-dependent cancer cell growth may be context-dependent. Our findings suggest that other mechanisms or pathways may bypass exclusive dependence on PHGDH in established human breast cancer xenografts, indicating that PHGDH is dispensable for the growth and maintenance and of tumors in vivo .
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.
Integrity signals
Registry
Cites
Statistics
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.
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?
PHGDH activity may not be required for proliferation in all PHGDH-amplified cancers; expression has been shown to be dispensable in a breast cancer xenograft model.
“However, PHGDH activity may not be a requirement for proliferation for all PHGDH-amplified cancers, as expression has been shown to be dispensable in a breast cancer xenograft model (Chen et al., 2013).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Chen et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Comprehensive molecular characterization of clear cell renal cell carcinoma
The Cancer Genome Atlas Research Network (2013) · Nature · doi:10.1038/nature12222 · Cited by 3,485 · see citing works
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820 · see citing works
Cancer cell metabolism: warburg and beyond
Hsu, P. P., & Sabatini, D. M. (2008) · Cell · doi:10.1016/j.cell.2008.08.021 · Cited by 2,452 · see citing works
Debnath, J., Muthuswamy, S. K., & Brugge, J. S. (2003) · Methods · doi:10.1016/s1046-2023(03)00032-x · Cited by 2,001 · see citing works
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., et al. (2011) · Nature · doi:10.1038/nature10350 · Cited by 1,683 · see citing works
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120 · see citing works
Tumor suppressors and cell metabolism: a recipe for cancer growth
Jones, R. G., & Thompson, C. B. (2009) · Genes & Development · doi:10.1101/gad.1756509 · Cited by 1,085 · see citing works
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation
Yang, W., Xia, Y., Ji, H., Zheng, Y., Liang, J., Huang, W., Gao, X., Aldape, K., & Lu, Z. (2011) · Nature · doi:10.1038/nature10598 · Cited by 1,033 · see citing works
Patra, K. C., Wang, Q., Bhaskar, P. T., Miller, L. L., Wang, Z., Wheaton, W. W., Chandel, N. S., Laakso, M., Muller, W. J., Allen, E. L., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.06.014 · Cited by 856 · see citing works
Pyruvate kinase type M2 and its role in tumor growth and spreading
Mazurek, S., Boschek, C. B., Hugo, F., & Eigenbrodt, E. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.04.009 · Cited by 812 · see citing works
Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells
Mazurek, S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.02.005 · Cited by 694 · see citing works
Serine is a natural ligand and allosteric activator of pyruvate kinase M2
Chaneton, B., Hillmann, P., Zheng, L., Martin, A. C. L., Maddocks, O. D. K., Chokkathukalam, A., Coyle, J. E., Jankevics, A., Holding, F. P., Vousden, K. H., et al. (2012) · Nature · doi:10.1038/nature11540 · Cited by 661 · see citing works
Lv, L., Dong, L., Zhao, D., Lin, R., Chu, Y., Zhang, H., Zha, Z., Liu, Y., Li, Z., Xu, Y., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.04.025 · Cited by 605 · see citing works
Enzymes of serine metabolism in normal, developing and neoplastic rat tissues
Snell, K. (1984) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(84)90021-9 · Cited by 267 · cited 1× · see citing works
“1A) [3].”
Cancer Cell MetabolismPreprint
Cairns, R. A., Harris, I. S., McCracken, S. A., & Mak, T. W. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.012856 · Cited by 223 · see citing works
Control of Nutrient Stress-Induced Metabolic Reprogramming by PKCζ in Tumorigenesis
Ma, L., Tao, Y., Durán, Á., Lladó, V., Galvez, A. S., Barger, J. F., Castilla, E. A., Chen, J., Yajima, T., Porollo, A., et al. (2013) · Cell · doi:10.1016/j.cell.2012.12.028 · Cited by 204 · see citing works
Self-citationSmall molecule activation of PKM2 in cancer cells induces serine auxotrophy
Kung, C., Hixon, J., Choe, S., Marks, K., Gross, S., Murphy, E., DeLaBarre, B., Cianchetta, G., Sethumadhavan, S., Wang, X., et al. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.07.021 · Cited by 192 · see citing works
M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth
Cortés-Cros, M., Hemmerlin, C., Ferretti, S., Zhang, J., Gounarides, J. S., Yin, H., Muller, A., Haberkorn, A., Chene, P., Sellers, W. R., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212780110 · Cited by 159 · see citing works
Self-citationLiu, J., Guo, S., Li, Q., Yang, L., Xia, Z.-B., Zhang, L., Huang, Z., & Zhang, N. (2012) · Journal of Neuro-Oncology · doi:10.1007/s11060-012-1018-x · Cited by 117 · see citing works
Cloning, sequencing and expression of rat liver 3-phosphoglycerate dehydrogenase
Achouri, Y., Rider, M. H., SCHAFTINGEN, E. V., & Robbi, M. (1997) · Biochemical Journal · doi:10.1042/bj3230365 · Cited by 93 · see citing works
Detection of point mutations of the Axin1 gene in colorectal cancers
Jin, L., Shao, Q., Luo, W., Ye, Z., Li, Q., & Lin, S. (2003) · International Journal of Cancer · doi:10.1002/ijc.11435 · Cited by 68 · see citing works
Purification and Properties of Chicken Liver D-3-Phosphoglycerate Dehydrogenase*
Walsh, D. A., & Sallach, H. J. (1965) · Biochemistry · doi:10.1021/bi00882a015 · Cited by 65 · see citing works
Targeting HSF1 sensitizes cancer cells to HSP90 inhibition
Chen, Y., Chen, J., Loo, A. T., Jaeger, S. A., Bagdasarian, L., Yu, J., Chung, F. S., Korn, J. M., Ruddy, D. A., Guo, R., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.991 · Cited by 60 · see citing works
Self-citationPKM2 and the Tricky Balance of Growth and Energy in Cancer
Macintyre, A. N., & Rathmell, J. C. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.003 · Cited by 60 · see citing works
Phosphoserine phosphatase distribution in normal and neoplastic rat tissues
Knox, W. E., Herzfeld, A., & Hudson, J. (1969) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(69)90381-6 · Cited by 38 · see citing works
Lund, K., Merrill, D. K., & Guynn, R. W. (1985) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(85)90268-1 · Cited by 33 · see citing works
Fan, M., Pfeffer, S. R., Lynch, H. T., Cassidy, P. B., Leachman, S. A., Pfeffer, L. M., & Kopelovich, L. (2013) · Oncotarget · doi:10.18632/oncotarget.786 · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Walsh MJ Brimacombe KR Anastasiou D Yu Y Israelsen WJ Hong BS Tempel W Dimov S Veith H Yang H Kung C Yen KE Dang L Salituro F Auld DS Park HW ML265: A potent PKM2 activator induces tetramerization and reduces tumor formation and size in a mouse xenograft model Probe Reports from the NIH Molecular Libraries Program. (Bethesda (MD) 2010 23905203
Cited by
Sorted by citations
One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239 · see citing works
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
Serine and one-carbon metabolism in cancer
Yang, M., & Vousden, K. H. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.81 · Cited by 992 · see citing works
A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate
Pacold, M. E., Brimacombe, K. R., Chan, S. H., Rohde, J. M., Lewis, C. A., Swier, L. J. Y. M., Possemato, R., Chen, W. W., Sullivan, L. B., Fiske, B. P., et al. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2070 · Cited by 553 · see citing works
The Diverse Functions of Non-Essential Amino Acids in Cancer
Choi, B.-H., & Coloff, J. L. (2019) · Cancers · doi:10.3390/cancers11050675 · Cited by 213 · see citing works
Wang, Q., Liberti, M. V., Liu, P., Deng, X., Liu, Y., Locasale, J. W., & Lai, L. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2016.11.013 · Cited by 147 · see citing works
High Expression of PHGDH Predicts Poor Prognosis in Non–Small Cell Lung Cancer
Zhu, J., Ma, J., Wang, X., Ma, T., Zhang, S., Wang, W., Zhou, X., & Shi, J. (2016) · Translational Oncology · doi:10.1016/j.tranon.2016.08.003 · Cited by 75 · see citing works
Rawat, V., Malvi, P., Della Manna, D., Yang, E. S., Bugide, S., Zhang, X., Gupta, R., & Wajapeyee, N. (2021) · Oncogene · doi:10.1038/s41388-021-01683-y · Cited by 43 · see citing works
Mattaini, K. R., Brignole, E. J., Kini, M., Davidson, S. M., Fiske, B. P., Drennan, C. L., & Vander Heiden, M. G. (2015) · Cancer & Metabolism · doi:10.1186/s40170-015-0131-7 · Cited by 38 · see citing works
- Authors
- Chen, J., Chung, F., Yang, G., Pu, M., Gao, H., Jiang, W., Yin, H., Capka, V., Kasibhatla, S., Laffitte, B., Jaeger, S., Pagliarini, R., Chen, Y., & Zhou, W.
- Affiliations
- Oncology, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
- Analytic Science, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
- Genomics Institute of the Novartis Research Foundation (US)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2013-11-26
- Volume
- 4
- Issue
- 12
- Pages
- 2502-2511
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC3926844
- OpenAlex
- W1934493757
- Cited by
- 82
- References
- 27
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 16 · 2020: 10 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 13 · 2015: 5 · 2014: 5
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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 › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- PHGDH, breast cancer, serine biosynthesis, tumor growth, tumor maintenance, aerobic glycolysis, Warburg effect, estrogen receptor-negative breast cancer, xenograft models, tumor cell proliferation
- MeSH terms
- Animals, Breast Neoplasms, Cell Transformation, Neoplastic, Female, Humans, RNA, Small Interfering, Cell Line, Tumor, Cell Growth Processes, Phosphoglycerate Dehydrogenase, Mice, Gene Knockdown Techniques, MCF-7 Cells, Heterografts
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
