The DOI matches its Crossref record; 26 of the 27 references it cites were found in a registry or an index.
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Open accessAbstract
Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.
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.
Integrity signals
Registry
Cites
Statistics
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.
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?
The cited source says what the claim attributes to it.
In the citing paper
“Functional PHGDH loss is toxic to tumor cells with PHGDH amplification or high serine biosynthetic flux (Locasale et al., 2011; Mattaini et al., 2015; Possemato et al., 2011; Zhang et al., 2017), and small-molecule inhibitors targeting PHGDH have been shown to inhibit serine synthesis and tumor proliferation in vitro and in xenograft cancer models (Mullarky et al., 2016; Pacold et al., 2016; Wang”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Possemato et al., 2011
In the citing paper
“Serine is present in plasma and can be taken up by cells via amino acid transporters, yet PHGDH expression and increased serine biosynthesis have been shown to be important for supporting cancer cell proliferation and survival in both in vitro and in vivo settings (Locasale et al., 2011; Possemato et al., 2011).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Possemato et al., 2011
In the citing paper
“Increased PHGDH gene expression leads to greater production of serine from glucose and is associated with specific subsets of breast cancer, lung adenocarcinoma, and melanoma (Locasale et al., 2011; Possemato et al., 2011; Zhang et al., 2017).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Possemato et al., 2011
In the citing paper
“More recently, it was found that increased expression of the serine synthesis enzyme phosphoglycerate dehydrogenase (PHGDH) in some cancers can result from copy number gain of a region on chromosome 1p (Beroukhim et al., 2010; Locasale et al., 2011; Possemato et al., 2011) or a consequence of oncogenic signaling, including NRF2 and ATF4 signaling (DeNicola et al., 2015), or hypoxia responses (Sam”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Possemato et al., 2011
In the citing paper
“A rate-limiting serine biosynthesis enzyme, 3-phosphoglycerate dehydrogenase (PHGDH), is frequently focally amplified in breast cancer and melanoma and is required for the growth of PHGDH-amplified cells in vitro as well as in vivo”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Possemato et al., 2011
In the citing paper
“Amplification of PHGDH has been observed in breast cancer and melanoma (65), and increased PHGDH expression can promote both enhanced serine biosynthesis and the proliferation of cancer cells (65, 66).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [66]
In the citing paper
“the region of chromosome 1p12 encoding PHGDH is amplified in a significant fraction of tumors”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Possemato et al., 2011
In the citing paper
“cell lines derived from these tumors tend to be highly dependent on PHGDH expression”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Possemato et al., 2011
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
A Gene-Expression Signature as a Predictor of Survival in Breast Cancer
van de Vijver, M. J., He, Y. D., Veer, L. V. ‘., Dai, H. A., Hart, A. A. M., Voskuil, D. W., Schreiber, G. J., Peterse, J. L., Roberts, C., Marton, M. J., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021967 · Cited by 6,474
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
Self-citationDeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622
Ben‐Porath, I., Thomson, M., Carey, V. J., Ge, R., Bell, G. W., Regev, A., & Weinberg, R. A. (2008) · Nature Genetics · doi:10.1038/ng.127 · Cited by 2,571
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464
Self-citationCancer 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 · cited 2×
“Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation (1,2).”
Self-citationRhodes, D. R., Sundaram, S. K., Mahavisno, V., Varambally, R., Yu, J., Briggs, B., Barrette, T. R., Anstett, M. J., Kincead-Beal, C., Kulkarni, P., et al. (2007) · Neoplasia · doi:10.1593/neo.07112 · Cited by 2,057
A Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen
Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., Piqani, B., Eisenhaure, T., Luo, B., Grenier, J. K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.040 · Cited by 1,804
Self-citationDissecting direct reprogramming through integrative genomic analysis
Mikkelsen, T. S., Hanna, J. H., Zhang, X., Ku, M., Wernig, M., Schorderet, P., Bernstein, B., Jaenisch, R., Lander, E. S., & Meissner, A. (2008) · Nature · doi:10.1038/nature07056 · Cited by 1,515
Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells
Marson, A., Levine, S. S., Cole, M. F., Frampton, G. M., Brambrink, T., Johnstone, S. E., Guenther, M. G., Johnston, W. K., Wernig, M., Newman, J. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.020 · Cited by 1,405
Cited by
Sorted by citations
Items 101–200 of 1,000
Glucose Metabolism in Cardiac Hypertrophy and Heart Failure
Tran, D. H., & Wang, Z. V. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.119.012673 · Cited by 336
Douce, J. L., Maugard, M., Veran, J., Matos, M., Jégo, P., Vigneron, P.-A., Faivre, É., Toussay, X., Vandenberghe, M. E., Balbastre, Y., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2020.02.004 · Cited by 336
Mullarky, E., Lucki, N. C., Beheshti Zavareh, R., Anglin, J. L., Gomes, A. P., Nicolay, B. N., Wong, J. C. Y., Christen, S., Takahashi, H., Singh, P. K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521548113 · Cited by 333
Proteomic maps of breast cancer subtypes
Tyanova, S., Albrechtsen, R., Kronqvist, P., Cox, J., Mann, M., & Geiger, T. (2016) · Nature Communications · doi:10.1038/ncomms10259 · Cited by 330
Rewiring urea cycle metabolism in cancer to support anabolism
Keshet, R., Szlosarek, P. W., Carracedo, A., & Erez, A. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0054-z · Cited by 330
Metabolic signatures of cancer cells and stem cells
Intlekofer, A. M., & Finley, L. W. S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0032-0 · Cited by 322
New aspects of the Warburg effect in cancer cell biology
Bensinger, S. J., & Christofk, H. R. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.02.003 · Cited by 322
Therapeutic targets in cancer cell metabolism and autophagy
Cheong, H., Lü, C., Lindsten, T., & Thompson, C. B. (2012) · Nature Biotechnology · doi:10.1038/nbt.2285 · Cited by 320
PML-Regulated Mitochondrial Metabolism Enhances Chemosensitivity in Human Ovarian Cancers
Gentric, G., Kieffer, Y., Mieulet, V., Goundiam, O., Bonneau, C., Némati, F., Hurbain, I., Raposo, G., Popova, T. G., Stern, M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.002 · Cited by 317
Serine restriction alters sphingolipid diversity to constrain tumour growth
Muthusamy, T., Cordes, T., Handzlik, M. K., You, L., Lim, E. W., Gengatharan, J. M., Pinto, A. F. M., Badur, M. G., Kolar, M. J., Wallace, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2609-x · Cited by 314
Dysregulated metabolism contributes to oncogenesis
Hirschey, M. D., DeBerardinis, R. J., Diehl, A. M., Drew, J. E., Frezza, C., Green, M. F., Jones, L. W., Ko, Y. H., Le, A., Lea, M. A., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.10.002 · Cited by 316
Sun, L., Song, L., Wan, Q., Wu, G., Li, X., Wang, Y., Wang, J., Liu, Z., Zhong, X., He, X., et al. (2015) · Cell Research · doi:10.1038/cr.2015.33 · Cited by 313
Resurgence of Serine: An Often Neglected but Indispensable Amino Acid
Kalhan, S. C., & Hanson, R. W. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.357194 · Cited by 312
Targeting amino acid metabolism for cancer therapy
Lukey, M. J., Katt, W. P., & Cerione, R. A. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2016.12.003 · Cited by 293
Tajan, M., Hennequart, M., Cheung, E. C., Zani, F., Hock, A. K., Legrave, N. M., Maddocks, O. D. K., Ridgway, R. A., Athineos, D., Suárez‐Bonnet, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20223-y · Cited by 312
Tumor suppressor p53 and metabolism
Liu, J., Zhang, C., Hu, W., & Feng, Z. (2018) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjy070 · Cited by 313
Metabolic Pathway Alterations that Support Cell ProliferationPreprint
Heiden, M. G. V., Lunt, S. Y., Dayton, T. L., Fiske, B. P., Israelsen, W. J., Mattaini, K. R., Vokes, N. I., Stephanopoulos, G. N., Cantley, L. C., Metallo, C. M., et al. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2012.76.010900 · Cited by 309
Current status and perspectives of patient-derived xenograft models in cancer research
Lai, Y., Wei, X., Lin, S., Qin, L., Cheng, L., & Li, P. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0470-7 · Cited by 308
Meng-Shian, C., Wang, S., Hsu, C., Yin, P., Yeh, T.-S., Lee, H., & Tseng, L. (2017) · Oncotarget · doi:10.18632/oncotarget.23055 · Cited by 306
Valencia, T., Kim, J. Y., Abu-Baker, S., Moscat-Pardos, J., Ahn, C. S., Reina-Campos, M., Duran, A., Castilla, E. A., Metallo, C. M., Diaz-Meco, M. T., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.05.004 · Cited by 304
Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses
Phang, J. M. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7350 · Cited by 302
Characterization of the development of the mouse cochlear epithelium at the single cell level
Kolla, L., Kelly, M. C., Mann, Z. F., Anaya, A., Ellis, K. A., Lemons, A. H. S., Palermo, A. T., So, K. S., Mays, J. C., Orvis, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16113-y · Cited by 294
Techniques to Monitor Glycolysis
TeSlaa, T. A., & Teitell, M. A. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-416618-9.00005-4 · Cited by 293
BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival
Gorrini, C., Baniasadi, P. S., Harris, I. S., Silvester, J., Inoue, S., Snow, B., Joshi, P. A., Wakeham, A., Molyneux, S. D., Martin, B., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20121337 · Cited by 289
Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells
Coloff, J. L., Murphy, J. P., Braun, C. R., Harris, I. S., Shelton, L. M., Kami, K., Gygi, S. P., Selfors, L. M., & Brugge, J. S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.016 · Cited by 288
Lin, R., Elf, S., Shan, C., Kang, H.-B., Ji, Q., Zhou, L., Hitosugi, T., Zhang, L., Zhang, S., Seo, J. H., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3255 · Cited by 287
Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE
Wang, Y., Eddy, J. A., & Price, N. D. (2012) · BMC Systems Biology · doi:10.1186/1752-0509-6-153 · Cited by 285
Vincent, E. E., Sergushichev, A., Griss, T., Gingras, M., Samborska, B., Ntimbane, T., Coelho, P. P., Blagih, J., Raissi, T. C., Choinière, L., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.08.013 · Cited by 281
Serine in plants: biosynthesis, metabolism, and functions
Ros, R., Muñoz-Bertomeu, J., & Krueger, S. (2014) · Trends in Plant Science · doi:10.1016/j.tplants.2014.06.003 · Cited by 279
A guide to 13C metabolic flux analysis for the cancer biologist
Antoniewicz, M. R. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0060-y · Cited by 278
Cancer, Oxidative Stress, and MetastasisPreprint
Gill, J. G., Piskounova, E., & Morrison, S. J. (2016) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2016.81.030791 · Cited by 278
The Influence of Metabolism on Drug Response in Cancer
Zaal, E. A., & Berkers, C. R. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00500 · Cited by 272
Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition
Ngo, B., Kim, E., Osorio-Vasquez, V., Doll, S., Bustraan, S., Liang, R. J., Luengo, A., Davidson, S. M., Ali, A., Ferraro, G. B., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1228 · Cited by 272
Self-citationL-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH
Intlekofer, A. M., Wang, B., Liu, H., Shah, H., Carmona-Fontaine, C., Rustenburg, A. S., Salah, S., Gunner, M. R., Chodera, J. D., Cross, J. R., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2307 · Cited by 268
Interplay between epigenetics and metabolism in oncogenesis: mechanisms and therapeutic approaches
Wong, C. C., Qian, Y., & Yu, J. Q. (2017) · Oncogene · doi:10.1038/onc.2016.485 · Cited by 266
Tedeschi, P. M., Markert, E. K., Gounder, M. K., Lin, H., Dvorzhinski, D., Dolfi, S. C., Chan, L. L.-Y., Qiu, J., DiPaola, R. S., Hirshfield, K. M., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.393 · Cited by 265
Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer
Bar-Peled, L., Kemper, E. K., Suciu, R. M., Vinogradova, E. V., Backus, K. M., Horning, B. D., Paul, T. A., Ichu, T.-A., Svensson, R. U., Olucha, J., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.051 · Cited by 262
Ducker, G. S., Ghergurovich, J. M., Mainolfi, N., Suri, V., Jeong, S. K., Hsin-Jung Li, S., Friedman, A., Manfredi, M. G., Gitai, Z., Kim, H., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1706617114 · Cited by 261
Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism
Gao, X., Lee, K., Reid, M. A., Sanderson, S. M., Qiu, C., Li, S., Liu, J., & Locasale, J. W. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.017 · Cited by 256
The ins and outs of serine and glycine metabolism in cancer
Geeraerts, S. L., Heylen, E., Keersmaecker, K. D., & Kampen, K. R. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00329-9 · Cited by 258
Kalyanaraman, B. (2017) · Redox Biology · doi:10.1016/j.redox.2017.04.018 · Cited by 254
Sullivan, M. R., Mattaini, K. R., Dennstedt, E. A., Nguyen, A. A., Sivanand, S., Reilly, M. F., Meeth, K. M., Muir, A., Darnell, A. M., Bosenberg, M., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.015 · Cited by 250
Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
Kurniawan, H., Franchina, D. G., Guerra, L., Bonetti, L., Soriano‐Baguet, L., Grusdat, M., Schlicker, L., Hunewald, O. E., Dostert, C., Merz, M. P., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.03.004 · Cited by 249
Metabolic reprogramming in triple-negative breast cancer
Wang, Z., Jiang, Q., & Dong, C. (2020) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2019.0210 · Cited by 248
Gluconeogenesis in cancer cells – Repurposing of a starvation-induced metabolic pathway?
Bluemel, G., Smolle, E., Olschewski, H., & Leithner, K. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.05.006 · Cited by 248
Heterogeneity in Cancer Metabolism: New Concepts in an Old Field
Gentric, G., Mieulet, V., & Mechta‐Grigoriou, F. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6750 · Cited by 248
Ding, J., Li, T., Wang, X., Zhao, E., Choi, J.-H., Yang, L., Zha, Y., Dong, Z., Huang, S., Asara, J. M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.004 · Cited by 246
Toward a better understanding of folate metabolism in health and disease
Zheng, Y., & Cantley, L. C. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20181965 · Cited by 246
Metabolic reprogramming in triple-negative breast cancer
Sun, X., Wang, M., Wang, M., Yu, X., Guo, J., Sun, T., Li, X., Yao, L., Dong, H., & Xu, Y. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00428 · Cited by 243
Metabolism, Activity, and Targeting of D- and L-2-Hydroxyglutarates
Ye, D., Guan, K.-L., & Xiong, Y. (2018) · Trends in Cancer · doi:10.1016/j.trecan.2017.12.005 · Cited by 242
Samanta, D., Park, Y., Andrabi, S. A., Shelton, L. M., Gilkes, D. M., & Semenza, G. L. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0530 · Cited by 242
RetractedGlutamine Metabolism in Cancer
Li, T., & Le, A. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-77736-8_2 · Cited by 242
Reid, M. A., Allen, A. E., Liu, S., Liberti, M. V., Liu, P., Liu, X., Dai, Z., Gao, X., Wang, Q., Liu, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07868-6 · Cited by 240
Fichman, Y., Gerdes, S., Kovács, H., Szabados, L., Zilberstein, A., & Csonka, L. N. (2014) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12146 · Cited by 239
Yang, Q., Liang, X., Sun, X., Zhang, L., Fu, X., Rogers, C. J., Berim, A., Zhang, S., Wang, S., Wang, B., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.010 · Cited by 237
Cancer Metabolism: Current Understanding and Therapies
Counihan, J. L., Grossman, E. A., & Nomura, D. K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00775 · Cited by 236
MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors
Birsoy, K., Wang, T., Possemato, R., Yilmaz, Ö. H., Koch, C. E., Chen, W. W., Hutchins, A., Gültekin, Y., Peterson, T. R., Carette, J. E., et al. (2012) · Nature Genetics · doi:10.1038/ng.2471 · Cited by 232
Self-citationKampen, K. R., Sulima, S. O., Vereecke, S., & Keersmaecker, K. D. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz637 · Cited by 231
Targeting arginine-dependent cancers with arginine-degrading enzymes: opportunities and challenges
Phillips, M. M., Sheaff, M. T., & Szlosarek, P. W. (2013) · Cancer Research and Treatment · doi:10.4143/crt.2013.45.4.251 · Cited by 229
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 229
Chang, S., Yim, S., & Park, H. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0230-6 · Cited by 228
Amino acids – A life between metabolism and signaling
Hausler, R., Ludewig, F., & Krueger, S. (2014) · Plant Science · doi:10.1016/j.plantsci.2014.09.011 · Cited by 228
Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored
Mikó, E., Kovàcs, T., Sebő, É., Tóth, J., Csonka, T., Ujlaki, G., Sipos, A., Szabó, J., Méhes, G., & Bai, P. (2019) · Cells · doi:10.3390/cells8040293 · Cited by 228
Lussey-Lepoutre, C., Hollinshead, K. E. R., Ludwig, C., Menara, M., Morin, A., Castro-Vega, L.-J., Parker, S. J., Janin, M., Martinelli, C., Ottolenghi, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms9784 · Cited by 227
Vazquez, A., Kamphorst, J. J., Markert, E. K., Schug, Z. T., Tardito, S., & Gottlieb, E. (2016) · Journal of Cell Science · doi:10.1242/jcs.181016 · Cited by 225
Dihydropyrimidine Accumulation Is Required for the Epithelial-Mesenchymal Transition
Shaul, Y. D., Freinkman, E., Comb, W. C., Cantor, J. R., Tam, W. L., Thiru, P., Kim, D., Kanarek, N., Pacold, M. E., Chen, W. W., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.032 · Cited by 223
Self-citationGlucose Oxidation Modulates Anoikis and Tumor Metastasis
Kamarajugadda, S., Stemboroski, L. N., Cai, Q., Simpson, N. E., Nayak, S., Tan, M., & Lu, J. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06248-11 · Cited by 222
Arginine Starvation Impairs Mitochondrial Respiratory Function in ASS1-Deficient Breast Cancer Cells
Qiu, F., Chen, Y.-R., Liu, X., Chu, C.-Y., Shen, L., Xu, J., Gaur, S., Forman, H. J., Zhang, H., Zheng, S. S., et al. (2014) · Science Signaling · doi:10.1126/scisignal.2004761 · Cited by 221
Pluripotent stem cell energy metabolism: an update
TeSlaa, T. A., & Teitell, M. A. (2014) · The EMBO Journal · doi:10.15252/embj.201490446 · Cited by 221
mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells
Pusapati, R. V., Daemen, A., Wilson, C., Sandoval, W. N., Gao, M., Haley, B., Baudy, A. R., Hatzivassiliou, G., Evangelista, M., & Settleman, J. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.02.018 · Cited by 221
PHGDH heterogeneity potentiates cancer cell dissemination and metastasis
Rossi, M., Altea‐Manzano, P., Demicco, M., Doglioni, G., Bornes, L., Fukano, M., Vandekeere, A., Cuadros, A. M., Fernández-García, J., Riera‐Domingo, C., et al. (2022) · Nature · doi:10.1038/s41586-022-04758-2 · Cited by 220
Formate metabolism in health and disease
Pietzke, M., Meiser, J., & Vazquez, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2019.05.012 · Cited by 218
Distinct Urinary Metabolic Profile of Human Colorectal Cancer
Cheng, Y., Xie, G., Chen, T., Qiu, Y., Zou, X., Zheng, M., Tan, B., Feng, B., Dong, T., He, P., et al. (2011) · Journal of Proteome Research · doi:10.1021/pr201001a · Cited by 218
Stable isotope-resolved metabolomics and applications for drug development
Fan, T. W. ‐., Lorkiewicz, P., Sellers, K., Moseley, H., Higashi, R. M., & Lane, A. N. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.12.007 · Cited by 215
Aslibekyan, S. W., Demerath, E. W., Mendelson, M., Zhi, D., Guan, W., Liang, L., Sha, J., Pankow, J. S., Liu, C., Irvin, M. R., et al. (2015) · Obesity · doi:10.1002/oby.21111 · Cited by 214
Li, F., Huangyang, P., Burrows, M., Guo, K., Riscal, R., Godfrey, J. T., Lee, K. E., Lin, N., Lee, P., Blair, I. A., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0511-2 · Cited by 216
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
Dietary Approaches to Cancer Therapy
Tajan, M., & Vousden, K. H. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.04.005 · Cited by 213
An expanded universe of cancer targets
Hahn, W. C., Bader, J. S., Braun, T. P., Califano, A., Clemons, P. A., Druker, B. J., Ewald, A. J., Fu, H., Jagu, S., Kemp, C. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.020 · Cited by 213
How do glycolytic enzymes favour cancer cell proliferation by nonmetabolic functions?
Lincet, H., & Icard, P. (2014) · Oncogene · doi:10.1038/onc.2014.320 · Cited by 212
Martinez‐Outschoorn, U., Sotgia, F., & Lisanti, M. P. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.03.002 · Cited by 211
Different Levels of Twist1 Regulate Skin Tumor Initiation, Stemness, and Progression
Beck, B., Lapouge, G., Rorive, S., Drogat, B., Desaedelaere, K., Delafaille, S., Dubois, C., Salmon, I. J., Willekens, K., Marine, J., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2014.12.002 · Cited by 210
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 209
Metabolic reprogramming by traditional Chinese medicine and its role in effective cancer therapy
Wang, S., Fu, J., Hao, H., Jiao, Y., Li, P., & Han, S. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105728 · Cited by 207
Human Phosphoglycerate Dehydrogenase Produces the Oncometabolite d -2-Hydroxyglutarate
Fan, J., Teng, X., Liu, L., Mattaini, K. R., Looper, R., Heiden, M. G. V., & Rabinowitz, J. D. (2014) · ACS Chemical Biology · doi:10.1021/cb500683c · Cited by 206
Metabolic crosstalk in the breast cancer microenvironment
Dias, A. S., Almeida, C. R., Helguero, L. A., & Duarte, I. F. (2019) · European Journal of Cancer · doi:10.1016/j.ejca.2019.09.002 · Cited by 206
Méndez‐Lucas, A., Hyroššová, P., Novellasdemunt, L., Viñals, F., & Perales, J. C. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.566927 · Cited by 205
Targeting amino acid metabolism in cancer growth and anti-tumor immune response
Ananieva, E. A. (2015) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v6.i4.281 · Cited by 203
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions
Vernieri, C., Casola, S., Foiani, M., Pietrantonio, F., de Braud, F., & Longo, V. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0615 · Cited by 202
TET proteins and 5‐methylcytosine oxidation in hematological cancers
Ko, M., An, J., Pastor, W. A., Koralov, S. B., Rajewsky, K., & Rao, A. (2014) · Immunological Reviews · doi:10.1111/imr.12239 · Cited by 202
HDAC inhibitors elicit metabolic reprogramming by targeting super-enhancers in glioblastoma models
Nguyen, T. T. T., Zhang, Y., Shang, E., Shu, C., Torrini, C., Zhao, J., Bianchetti, E., Mela, A., Humala, N., Mahajan, A., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci129049 · Cited by 202
R�os, S., Santos, C. R., Moco, S., Baenke, F., Kelly, G. P., Howell, M. T., Zamboni, N., & Schulze, A. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0234 · Cited by 201
Diverting Glycolysis to Combat Oxidative Stress
Mullarky, E., & Cantley, L. C. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0_1 · Cited by 197
An Integrated Genomic Screen Identifies LDHB as an Essential Gene for Triple-Negative Breast Cancer
McCleland, M. L., Adler, A. S., Shang, Y., Hunsaker, T., Truong, T., Peterson, D., Torres, E., Li, L., Haley, B., Stéphan, J.-P., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1098 · Cited by 195
Darnell, A. M., Subramaniam, A. R., & O’Shea, E. K. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.041 · Cited by 195
Glutamine Metabolism Is Required for Collagen Protein Synthesis in Lung Fibroblasts
Hamanaka, R. B., O’Leary, E. M., Witt, L. J., Tian, Y., Gökalp, G. A., Meliton, A. Y., Dulin, N. O., & Mutlu, G. M. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0008oc · Cited by 195
Filipp, F. V., Scott, D. A., Ronai, Z. A., Osterman, A. L., & Smith, J. W. (2012) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2012.00989.x · Cited by 193
Small 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
Self-citationMetabolism‐associated molecular classification of hepatocellular carcinoma
Yang, C. G., Huang, X., Liu, Z., Qin, W., & Wang, C. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12639 · Cited by 192
Famine versus feast: understanding the metabolism of tumors in vivo
Mayers, J. R., & Heiden, M. G. V. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.01.004 · Cited by 190
Metadata
- Authors
- 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., Chen, W. W., Barrett, F. G., Stransky, N., Tsun, Z.-Y., Cowley, G. S., Barretina, J., Kalaany, N. Y., Hsu, P. P., Ottina, K., Chan, A. M., Yuan, B., Garraway, L. A., Root, D. E., Mino-Kenudson, M., Brachtel, E. F., Driggers, E. M., & Sabatini, D. M.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Agios Pharmaceuticals (United States) (US)
- Broad Institute (US)
- Harvard University (US)
- Corresponding author
- Sabatini, David M.
- ORCID
- Possemato, Richard
- Shaul, Yoav D.
- Pacold, Michael E.
- Kim, Dohoon
- Birsoy, Kıvanç
- Sethumadhavan, Shalini
- Jang, Hyun G.
- Jha, Abhishek K.
- Chen, Walter W.
- Barrett, Francesca G.
- Stransky, Nicolas
- Cowley, Glenn S.
- Barretina, Jordi
- Kalaany, Nada Y.
- Hsu, Peggy P.
- Yuan, Bingbing
- Garraway, Levi A.
- Root, David E.
- Mino-Kenudson, Mari
- Brachtel, Elena F.
- Sabatini, David M.
- Venue
- Nature
- Published
- 2011-08
- Volume
- 476
- Issue
- 7360
- Pages
- 346-350
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3353325
- OpenAlex
- W2022899908
- Cited by
- 1,683
- References
- 27
- Citations by year
- 2026: 72 · 2025: 111 · 2024: 120 · 2023: 116 · 2022: 138 · 2021: 167 · 2020: 137 · 2019: 126 · 2018: 93 · 2017: 97 · 2016: 125 · 2015: 93 · 2014: 109 · 2013: 72 · 2012: 87
- FWCI
- 31.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- PMC
- Funders
- Howard Hughes Medical Institute
- W. M. Keck Foundation
- Alexander and Margaret Stewart Trust
- Life Sciences Research Foundation
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Institutes of Health
- National Cancer Institute (CA103866, R01CA103866, R01CA129105)
- National Institute of General Medical Sciences (T32GM007753)
- 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, cancer metabolism, breast cancer xenografts, estrogen receptor-negative breast cancer, alpha-ketoglutarate, glutamine metabolism, TCA cycle, anaplerosis, tumor metabolic reprogramming, anticancer drug targets, cell proliferation
- MeSH terms
- Animals, Breast Neoplasms, Citric Acid Cycle, Humans, Ketoglutaric Acids, Melanoma, Neoplasm Transplantation, Serine, Biomarkers, Tumor, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Glutamic Acid, Genomics, RNA Interference, Cell Line, Tumor, Cell Proliferation, Phosphoglycerate Dehydrogenase, Mice
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
