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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.
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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
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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
“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
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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
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Stine, Z. E., & Dang, C. V. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.844093 · Cited by 44
Mohamed, A. D., Sun, C., Mello, V. D., Selfe, J., Missiaglia, E., SHIPLEY, J. M., Murray, G. I., Zammit, P. S., & Wackerhage, H. (2016) · The Journal of Pathology · doi:10.1002/path.4745 · Cited by 44
Badur, M. G., & Metallo, C. M. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.11.013 · Cited by 44
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Mazat, J., & Ransac, S. (2019) · Metabolites · doi:10.3390/metabo9050081 · Cited by 44
Liao, K. L., Deng, S., Xu, L., Pan, W., Yang, S., Zheng, F., Wu, X., Hu, H., Liu, Z., Luo, J., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2060 · Cited by 44
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Haferkamp, S., Drexler, K., Federlin, M., Schlitt, H. J., Berneburg, M., Adamski, J., Gaumann, A. K. A., Geissler, E. K., Ganapathy, V., Parkinson, E. K., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.602476 · Cited by 44
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
Deng, X., Xie, B., Li, Q., Xiao, Y., Hu, Z., Deng, X., Fang, P., Dong, C., Zhou, H.-B., & Huang, J. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00525 · Cited by 43
Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance
Lei, P., Wang, W., Sheldon, M., Sun, Y., Yao, F., & Ma, L. (2023) · Cancers · doi:10.3390/cancers15133390 · Cited by 45
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Cortellino, S., & Longo, V. D. (2023) · Cancers · doi:10.3390/cancers15153898 · Cited by 43
Baumert, P., Mäntyselkä, S., Schönfelder, M., Heiber, M., Jacobs, M. J., Swaminathan, A., Minderis, P., Dirmontas, M., Kleigrewe, K., Meng, C., et al. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13468 · Cited by 43
Possik, P. A., Müller, J., Gerlach, C., Kenski, J. C. N., Huang, X., Shahrabi, A., Krijgsman, O., Song, J., Smit, M. A., Gerritsen, B., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.024 · Cited by 43
Yasuda, S., Sugiura, H., Katsurabayashi, S., Shimada, T., Tanaka, H., Takasaki, K., Iwasaki, K., Kobayashi, T., Hino, O., & Yamagata, K. (2014) · Scientific Reports · doi:10.1038/srep05155 · Cited by 43
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Young, J., Duckwall, C., & Murphy, T. A. (2013) · Journal of Carcinogenesis · doi:10.4103/1477-3163.115422 · Cited by 43
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Yoon, S., Kim, J. G., Seo, A. N., Park, S. Y., Kim, H. J., Park, J. S., Choi, G., Jeong, J. Y., Jun, D. Y., Yoon, G. S., et al. (2015) · Oncology · doi:10.1159/000439571 · Cited by 43
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Ding, Z., Ericksen, R. E., Lee, Q. Y., & Han, W. (2021) · Amino Acids · doi:10.1007/s00726-021-02961-5 · Cited by 43
Genetic selection for enhanced serine metabolism in cancer development
Locasale, J. W., & Cantley, L. C. (2011) · Cell Cycle · doi:10.4161/cc.10.22.18224 · Cited by 43
Chan, F.-F., Kwan, K. K., Seoung, D.-H., Chin, D. W., Ng, I. O., Wong, C. C., & Wong, C. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.10.025 · Cited by 42
Sanders, E. B., & Diehl, S. (2015) · Oncoscience · doi:10.18632/oncoscience.128 · Cited by 43
Unterlass, J. E., Baslé, A., Blackburn, T. J., Tucker, J. A., Cano, C., Noble, M. E. M., & Curtin, N. J. (2016) · Oncotarget · doi:10.18632/oncotarget.11487 · Cited by 42
Unterlass, J. E., Wood, R. J., Baslé, A., Tucker, J. A., Cano, C., Noble, M. E. M., & Curtin, N. J. (2017) · Oncotarget · doi:10.18632/oncotarget.22327 · Cited by 42
Davis, R. J., Gönen, M., Margineantu, D. H., Handeli, S., Swanger, J., Hoellerbauer, P., Paddison, P. J., Gu, H., Raftery, D., Grim, J. E., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718338115 · Cited by 42
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Frost, F. G., Cherukuri, P. F., Milanovich, S. J., & Boerkoel, C. F. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14746 · Cited by 42
Hight, S. K., Mootz, A. A., Kollipara, R. K., McMillan, E. A., Yenerall, P. M., Yoichi, O., Li, L.-S., Avila, K., Peyton, M., Rodriguez‐Canales, J., et al. (2020) · Neoplasia · doi:10.1016/j.neo.2020.04.005 · Cited by 42
Brown, D. M., Williams, H., Ryan, K. J. P., Wilson, T. L., Daniel, Z. C. T. R., Mareko, M. H. D., Emes, R. D., Harris, D. W., Jones, S., Wattis, J. A. D., et al. (2016) · Scientific Reports · doi:10.1038/srep28693 · Cited by 42
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Ashkavand, Z., O’Flanagan, C. H., Hennig, M., Du, X., Hursting, S. D., & Krupenko, S. A. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0317 · Cited by 41
Li, N., & Liu, X. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s238920 · Cited by 41
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Patra, S., Elahi, N., Armorer, A., Arunachalam, S., Omala, J., Hamid, I., Ashton, A. W., Joyce, D. A., Jiao, X., & Pestell, R. G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.700629 · Cited by 43
Ros, R., Cascales‐Miñana, B., Segura, J., Anoman, A. D., Toujani, W., Flores‐Tornero, M., Rosa‐Téllez, S., & Muñoz‐Bertomeu, J. (2012) · Plant Biology · doi:10.1111/j.1438-8677.2012.00682.x · Cited by 41
Shema, R., Kulicke, R., Cowley, G. S., Stein, R., Root, D. E., & Heiman, M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417231112 · Cited by 41
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Suchorolski, M. T., Paulson, T. G., Sanchez, C. A., Hockenbery, D., & Reid, B. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056884 · Cited by 40
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Huang, G., Hucek, D. G., Cierpicki, T., & Grembecka, J. E. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115802 · Cited by 40
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Gang, B. P., Dilda, P. J., Hogg, P. J., & Blackburn, A. C. (2014) · Cancer Biology & Therapy · doi:10.4161/15384047.2014.955992 · Cited by 40
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Schnackenberg, L. K., Pence, L. M., Vijay, V., Moland, C. L., George, N. I., Cao, Z., Yu, L., Fuscoe, J. C., Beger, R. D., & Desai, V. G. (2016) · Journal of Applied Toxicology · doi:10.1002/jat.3307 · Cited by 40
Li, M., Bu, X., Cai, B., Liang, P., Li, K., Qu, X., & Shen, L. (2018) · Oncology Reports · doi:10.3892/or.2018.6882 · Cited by 40
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Nguyen, M. Q., Teh, J. L. F., Purwin, T. J., Chervoneva, I., Davies, M. A., Nathanson, K. L., Cheng, P. F., Levesque, M. P., Dummer, R., & Aplin, A. E. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.02.047 · Cited by 40
Zhu, W., Ding, Q., Wang, L., Xu, G., Diao, Y., Qu, S., Chen, S., & Shi, Y. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108212 · Cited by 40
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Sun, W. Y., Zhao, E., & Cui, H. (2022) · International Journal of Cancer · doi:10.1002/ijc.34353 · Cited by 39
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Drexler, K., Schmidt, K. M., Jordan, K., Federlin, M., Milenkovic, V. M., Liebisch, G., Artati, A., Schmidl, C., Madej, M. G., Tokarz, J., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202000903 · Cited by 39
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Wu, Q., Li, J., Sun, S., Chen, X., Zhang, H., Li, B., & Sun, S. (2017) · Bioscience Reports · doi:10.1042/bsr20171072 · Cited by 38
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Do, L. K., Lee, H. M., Ha, Y., Lee, C., & Kim, J. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115529 · Cited by 38
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Stegen, S., Loopmans, S., Stockmans, I., Moermans, K., Carmeliet, P., & Carmeliet, G. (2022) · Bone Research · doi:10.1038/s41413-021-00185-7 · Cited by 38
Choi, B.-H., Rawat, V., Högström, J., Burns, P. A., Conger, K. O., Özgürses, M. E., Patel, J. M., Mehta, T. S., Warren, A., Selfors, L. M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110278 · Cited by 38
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Shu, Y., Hao, Y., Feng, J., Liu, H., Li, S., Feng, J., Jiang, Z., Ye, L., Zhou, Y., Sun, Y., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022111550 · Cited by 38
Nolan-Stevaux, O., Tedesco, D., Ragan, S. P., Makhanov, M., Chenchik, A. A., Ruefli-Brasse, A. A., Quon, K. C., & Kassner, P. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067316 · Cited by 38
Strezoska, Ž., Licon, A., Haimes, J. D., Spayd, K. J., Patel, K. M., Sullivan, K., Jastrzebski, K., Simpson, K. J., Leake, D., Smith, A. V. B., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042341 · Cited by 38
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Novak, J. S. S., Baksh, S. C., & Fuchs, E. V. (2021) · Genes & Development · doi:10.1101/gad.346973.120 · Cited by 38
Jia, Q., Cui, C., Deng, Q., Wang, L., Chen, R., Zhai, D., Xie, L., & Yu, J. (2018) · Oncology Letters · doi:10.3892/ol.2018.9400 · Cited by 37
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Arora, G., Tiwari, P., Mandal, R. S., Gupta, A., Sharma, D., Saha, S., & Singh, R. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.597682 · Cited by 37
Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer
Roy, D., Mondal, S., Wang, C., He, X., Khurana, A., Giri, S., Hoffmann, R. G., Jung, D., Kim, S. H., Chini, E. N., et al. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-13 · Cited by 37
Paiardini, A., Fiascarelli, A., Rinaldo, S., Daidone, F., Giardina, G., Koes, D. R., Parroni, A., Montini, G., Marani, M., Paone, A., et al. (2015) · ChemMedChem · doi:10.1002/cmdc.201500028 · Cited by 37
Phosphoglycerate Dehydrogenase: Potential Therapeutic Target and Putative Metabolic Oncogene
Zogg, C. K. (2014) · Journal of Oncology · doi:10.1155/2014/524101 · Cited by 36
Localization of NADPH Production: A Wheel within a Wheel
Maddocks, O. D. K., Labuschagne, C. F., & Vousden, K. H. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.07.001 · Cited by 36
Cancer's sweet tooth for serine
Luo, J. (2011) · Breast Cancer Research · doi:10.1186/bcr2932 · Cited by 36
Regulation of mitochondrial apoptosis by Pin1 in cancer and neurodegeneration
Sorrentino, G., Comel, A., Mantovani, F., & Sal, G. D. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.08.003 · Cited by 36
Monitoring the dynamics of clonal tumour evolution in vivo using secreted luciferases
Charles, J. P., Fuchs, J., Hefter, M., Vischedyk, J. B., Kleint, M., Vogiatzi, F., Schäfer, J., Nist, A., Timofeev, O. N., Wanzel, M., et al. (2014) · Nature Communications · doi:10.1038/ncomms4981 · Cited by 36
Gromova, I., Gromov, P., Honma, N., Kumar, S., Rimm, D. L., Talman, M., Wielenga, V. T., & Moreira, J. M. A. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.05.003 · Cited by 36
Ohshima, K., Nojima, S., Tahara, S., Kurashige, M., Hori, Y., Hagiwara, K., Okuzaki, D., Oki, S., Wada, N., Ikeda, J.-I., et al. (2017) · Scientific Reports · doi:10.1038/srep45504 · Cited by 36
One-Carbon Metabolism: Biological Players in Epithelial Ovarian Cancer
Rizzo, A., Napoli, A., Roggiani, F., Tomassetti, A., Bagnoli, M., & Mezzanzanica, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072092 · Cited by 36
SLC25A32 sustains cancer cell proliferation by regulating flavin adenine nucleotide (FAD) metabolism
Santoro, V., Kovalenko, I., Vriens, K., Christen, S., Bernthaler, A., Haegebarth, A., Fendt, S., & Christian, S. (2020) · Oncotarget · doi:10.18632/oncotarget.27486 · Cited by 36
Tan, B., Jaulin, A., Bund, C., Outilaft, H., Wendling, C., Chenard, M., Alpy, F., Çiçek, A. E., Namer, I. J., Tomasetto, C., et al. (2020) · Cancers · doi:10.3390/cancers12092357 · Cited by 36
Zhang, G., Yang, Y., Hu, H., Liu, K., Li, B., Zhu, Y., Wang, Z., Wu, Q., & Mei, Y. (2021) · Oncogene · doi:10.1038/s41388-021-01749-x · Cited by 36
The Heterogeneity of Breast Cancer Metabolism
Tan, J., & Le, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-65768-0_6 · Cited by 36
Metabolic Flexibility Is a Determinant of Breast Cancer Heterogeneity and Progression
Fukano, M., Park, M., & Deblois, G. (2021) · Cancers · doi:10.3390/cancers13184699 · Cited by 36
Metabolic therapy and bioenergetic analysis: The missing piece of the puzzle
Duraj, T., Carrión-Navarro, J., Seyfried, T. N., Garcia‐Romero, N., & Ayuso‐Sacido, Á. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101389 · Cited by 36
Franco, C. N., Seabrook, L. J., Nguyen, S. T., Leonard, J. T., & Albrecht, L. V. (2022) · Metabolites · doi:10.3390/metabo12100961 · Cited by 36
Targeting Mitochondria with ClpP Agonists as a Novel Therapeutic Opportunity in Breast Cancer
Wedam, R., Greer, Y. E., Wisniewski, D. J., Weltz, S., Kundu, M., Voeller, D. M., & Lipkowitz, S. (2023) · Cancers · doi:10.3390/cancers15071936 · Cited by 36
PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma.
D’Avola, A., Legrave, N. M., Tajan, M., Chakravarty, P., Shearer, R. L., King, H. W., Kľučková, K., Cheung, E. C., Clear, A. J., Gunawan, A. S., et al. (2022) · Figshare · doi:10.25418/crick.19723081 · Cited by 36
Meseure, D., Alsibai, K. D., & Nicolas, A. (2014) · Cancer Microenvironment · doi:10.1007/s12307-014-0158-2 · Cited by 36
Altered Mitochondrial Signalling and Metabolism in Cancer
Chattopadhyay, E., & Roy, B. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00043 · Cited by 36
Sharif, T., Martell, E., Dai, C., Ghassemi-Rad, M. S., Lee, K., Singh, S. K., Weaver, I. C. G., & Gujar, S. A. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0997-8 · Cited by 36
A comprehensive review on signaling attributes of serine and serine metabolism in health and disease
Wu, D., Zhang, K., Khan, F. A., Pandupuspitasari, N. S., Guan, K., Sun, F., & Huang, C. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.129607 · Cited by 35
Nutrient requirements of organ-specific metastasis in breast cancer
Abbott, K. L., Subudhi, S., Ferreira, R., Gültekin, Y., Steinbuch, S. C., Munim, M. B., Ramesh, D. L., Honeder, S. E., Kumar, A. S., Wu, M., et al. (2026) · Nature · doi:10.1038/s41586-025-09898-9 · Cited by 35
Azacoccone E inhibits cancer cell growth by targeting 3-phosphoglycerate dehydrogenase
Guo, J., Gu, X., Zheng, M., Zhang, Y., Chen, L., & Li, H. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.02.037 · Cited by 35
Xu, L., Wang, L., Zhou, L., Dorfman, R. G., Pan, Y., Tang, D., Wang, Y., Yin, Y., Jiang, C., Zou, X., et al. (2019) · Neoplasia · doi:10.1016/j.neo.2019.03.002 · Cited by 35
Metabolome Wide Association Study of serum DDT and DDE in Pregnancy and Early Postpartum
Hu, X. Y., Li, S., Cirillo, P. M., Krigbaum, N. Y., Tran, V., Ishikawa, T., Merrill, M. A. L., Jones, D. P., & Cohn, B. A. (2019) · Reproductive Toxicology · doi:10.1016/j.reprotox.2019.05.059 · Cited by 35
Alptekin, A., Ye, B., Yu, Y., Poole, C. J., van Riggelen, J., Zha, Y., & Ding, H. (2019) · Oncogene · doi:10.1038/s41388-019-0967-3 · Cited by 35
Han, M., Piorońska, W., Wang, S., Nwosu, Z. C., Sticht, C., Wang, S., Gao, Y. L., Ebert, M., Dooley, S., & Meyer, C. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2295-5 · Cited by 35
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
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