Mouse Genetics Suggests Cell-Context Dependency for Myc-Regulated Metabolic Enzymes during Tumorigenesis
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c-Myc (hereafter called Myc) belongs to a family of transcription factors that regulates cell growth, cell proliferation, and differentiation. Myc initiates the transcription of a large cast of genes involved in cell growth by stimulating metabolism and protein synthesis. Some of these, like those involved in glycolysis, may be part of the Warburg effect, which is defined as increased glucose uptake and lactate production in the presence of adequate oxygen supply. In this study, we have taken a mouse-genetics approach to challenge the role of select Myc-regulated metabolic enzymes in tumorigenesis in vivo. By breeding λ-Myc transgenic mice, Apc(Min) mice, and p53 knockout mice with mouse models carrying inactivating alleles of Lactate dehydrogenase A (Ldha), 3-Phosphoglycerate dehydrogenase (Phgdh) and Serine hydroxymethyltransferase 1 (Shmt1), we obtained offspring that were monitored for tumor development. Very surprisingly, we found that these genes are dispensable for tumorigenesis in these genetic settings. However, experiments in fibroblasts and colon carcinoma cells expressing oncogenic Ras show that these cells are sensitive to Ldha knockdown. Our genetic models reveal cell context dependency and a remarkable ability of tumor cells to adapt to alterations in critical metabolic pathways. Thus, to achieve clinical success, it will be of importance to correctly stratify patients and to find synthetic lethal combinations of inhibitors targeting metabolic enzymes.
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The expression of SBP enzymes is up-regulated in Myc-driven lymphomas.
“The expression of SBP enzymes is up-regulated in Myc-driven lymphomas (68); thus, we hypothesize that TEFF cells may actively engage the SBP upon activation, even in the”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [68]
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Cites
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425 · 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
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124 · 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
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635 · see citing works
Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression
Le, A., Cooper, C. R., Gouw, A. M., Dinavahi, R., Maitra, A., Deck, L. M., Royer, R. E., Jagt, D. L. V., Semenza, G. L., & Dang, C. V. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914433107 · Cited by 1,528 · see citing works
Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization
Zindy, F., Eischen, C. M., Randle, D. H., Kamijo, T., Cleveland, J. L., Sherr, C. J., & Roussel, M. F. (1998) · Genes & Development · doi:10.1101/gad.12.15.2424 · Cited by 1,245 · see citing works
HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
David, C. J., Chen, M., Assanah, M., Canoll, P., & Manley, J. L. (2010) · Nature · doi:10.1038/nature08697 · Cited by 1,179 · 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
c-Myc transactivation of <i>LDH-A</i> : Implications for tumor metabolism and growth
Shim, H., Dolde, C., Lewis, B. C., Wu, C.-S., Dang, G., Jungmann, R. A., Dalla-Favera, R., & Dang, C. V. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6658 · Cited by 1,092 · see citing works
Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster
Dews, M., Homayouni, A., Yu, D., Murphy, D. A., Sevignani, C., Wentzel, E. A., Furth, E. E., Lee, W. M., Enders, G. H., Mendell, J. T., et al. (2006) · Nature Genetics · doi:10.1038/ng1855 · Cited by 1,049 · see citing works
MYC-Induced Cancer Cell Energy Metabolism and Therapeutic Opportunities
Dang, C. V., Le, A., & Gao, P. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0889 · Cited by 934 · see citing works
Eilers, M., & Eisenman, R. N. (2008) · Genes & Development · doi:10.1101/gad.1712408 · Cited by 927 · see citing works
Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2
Strasser, A., Harris, A. W., Bath, M. L., & Cory, S. (1990) · Nature · doi:10.1038/348331a0 · Cited by 905 · see citing works
Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation
Wang, J.-B., Erickson, J. W., Fuji, R., Ramachandran, S., Gao, P., Dinavahi, R., Wilson, K. F., Ambrosio, A. L. B., Dias, S. M. G., Dang, C. V., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.08.009 · Cited by 821 · see citing works
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J., & Cleveland, J. L. (1999) · Genes & Development · doi:10.1101/gad.13.20.2658 · Cited by 819 · see citing works
The ornithine decarboxylase gene is a transcriptional target of c-Myc.
Bello-Fernández, C., Packham, G., & Cleveland, J. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.16.7804 · Cited by 783 · see citing works
Multifaceted roles of glycolytic enzymes
Kim, J., & Dang, C. V. (2005) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.01.005 · Cited by 682 · see citing works
Kim, J., Woo, A., Chu, J., Snow, J. W., Fujiwara, Y., Kim, C., Cantor, A., & Orkin, S. (2010) · Cell · doi:10.1016/j.cell.2010.09.010 · Cited by 670 · see citing works
Myc deletion rescues Apc deficiency in the small intestine
Sansom, O. J., Méniel, V. S., Muncan, V., Phesse, T. J., Wilkins, J. A., Reed, K. R., Vass, J. K., Athineos, D., Clevers, H. C., & Clarke, A. R. (2007) · Nature · doi:10.1038/nature05674 · Cited by 614 · see citing works
Zheng, L., Roeder, R. G., & Luo, Y. (2003) · Cell · doi:10.1016/s0092-8674(03)00552-x · Cited by 534 · see citing works
Meyskens, F. L., McLaren, C. E., Pelot, D., Fujikawa-Brooks, S., Carpenter, P. M., Hawk, E. T., Kelloff, G. J., Lawson, M. J., Kidao, J., McCracken, J., et al. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0042 · Cited by 518 · see citing works
c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progressionPreprint
Baudino, T. A., McKay, C., Pendeville, H., Nilsson, J. A., Maclean, K. H., White, E. L., Davis, A. C., Ihle, J. N., & Cleveland, J. L. (2002) · Genes & Development · doi:10.1101/gad.1024602 · Cited by 516 · see citing works
Self-citationReversible Activation of c-Myc in Skin
Pelengaris, S., Littlewood, T. D., Khan, M., Elia, G., & Evan, G. I. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80350-0 · Cited by 469 · see citing works
INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53
Schmitt, C. A., McCurrach, M. E., de Stanchina, E., Wallace-Brodeur, R. R., & Lowe, S. W. (1999) · Genes & Development · doi:10.1101/gad.13.20.2670 · Cited by 458 · see citing works
Distinct Thresholds Govern Myc's Biological Output In Vivo
Murphy, D. J., Junttila, M. R., Pouyet, L., Karnezis, A., Shchors, K., Bui, D. A., Brown-Swigart, L., Johnson, L., & Evan, G. I. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.10.018 · Cited by 456 · see citing works
Kitada, S., Leone, M., Sareth, S., Zhai, D., Reed, J. C., & Pellecchia, M. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm030190z · Cited by 382 · see citing works
Analysis of genomic targets reveals complex functions of MYC
Patel, J. H., Loboda, A. P., Showe, M. K., Showe, L. C., & McMahon, S. B. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1393 · Cited by 306 · see citing works
Targeting aspartate aminotransferase in breast cancer
Thornburg, J. M., Nelson, K. K., Clem, B. F., Lane, A. N., Arumugam, S., Simmons, A., Eaton, J. W., Telang, S., & Chesney, J. (2008) · Breast Cancer Research · doi:10.1186/bcr2154 · Cited by 288 · see citing works
A unique glucose-dependent apoptotic pathway induced by c-Myc
Shim, H., Chun, Y. S., Lewis, B. C., & Dang, C. V. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1511 · Cited by 286 · see citing works
ODC1 Is a Critical Determinant of MYCN Oncogenesis and a Therapeutic Target in Neuroblastoma
Hogarty, M. D., Norris, M. D., Davis, K., Liu, X., Evageliou, N. F., Hayes, C. S., Pawel, B., Guo, R. J., Zhao, H., Sekyere, E. O., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6866 · Cited by 263 · see citing works
Xie, H., Valera, V., Merino, M. J., Amato, A. M., Signoretti, S., Linehan, W. M., Sukhatme, V. P., & Seth, P. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-1049 · Cited by 232 · see citing works
HER‐2/ <i>neu</i> Signal Transduction in Human Breast and Ovarian Cancer
Reese, D. M., & Slamon, D. J. (1997) · STEM CELLS · doi:10.1002/stem.150001 · Cited by 229 · see citing works
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
Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation
Nilsson, J. A., Keller, U. B., Baudino, T. A., Yang, C., Norton, S., Old, J. B., Nilsson, L. M., Neale, G. A. M., Kramer, D. L., Porter, C. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.03.036 · Cited by 210 · see citing works
Self-citationKovalchuk, A. L., Qi, C., Torrey, T. A., Taddesse-Heath, L., Feigenbaum, L., Park, S. S., Gerbitz, A., Klobeck, G., Hoertnagel, K., Polack, A., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.8.1183 · Cited by 204 · see citing works
Self-citationNikiforov, M. A., Chandriani, S. J., O’Connell, B. C., Petrenko, O., Kotenko, I., Beavis, A. J., Sedivy, J. M., & Cole, M. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.16.5793-5800.2002 · Cited by 201 · see citing works
Genomic instability and apoptosis are frequent in p53 deficient young mice
Fukasawa, K., Wiener, F., Woude, G. F. V., & Mai, S. (1997) · Oncogene · doi:10.1038/sj.onc.1201482 · Cited by 194 · see citing works
Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184 · see citing works
Miltenberger, R. J., Sukow, K. A., & Farnham, P. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.5.2527 · Cited by 172 · see citing works
Lin, J., Chen, Y., Huang, Y.-T., & Lin‐Shiau, S. (1997) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(1997)28/29+ · Cited by 163 · see citing works
Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., Tanaka, H., Hashikawa, T., Itohara, S., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300507200 · Cited by 161 · cited 1× · see citing works
“Since Phgdh is essential for neurogenesis [30], Phgdh null embryos die at around embryonic day (E) 13.”
BackgroundQing, G., Skuli, N., Mayes, P. A., Pawel, B., Martinez, D., Maris, J. M., & Simon, M. C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0740 · Cited by 157 · see citing works
c-Myc induces the expression and activity of ornithine decarboxylase.
Wagner, A. J., Meyers, C., Laimins, L. A., & Hay, N. (1993) · PubMed · Cited by 154 · see citing works
Jacoby, R. F., Cole, C. E., Tutsch, K. D., Newton, M. A., Kelloff, G. J., Hawk, E. T., & Lubet, R. A. (2000) · PubMed · Cited by 152 · see citing works
MacFarlane, A. J., Liu, X., Perry, C. A., Flodby, P., Allen, R. H., Stabler, S. P., & Stover, P. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802671200 · Cited by 148 · see citing works
The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry
Morrish, F. M., Neretti, N., Sedivy, J. M., & Hockenbery, D. M. (2008) · Cell Cycle · doi:10.4161/cc.7.8.5739 · Cited by 130 · see citing works
Chemoprevention of prostate carcinogenesis by alpha-difluoromethylornithine in TRAMP mice.
Gupta, S., Ahmad, N., Marengo, S. R., MacLennan, G. T., Greenberg, N. M., & Mukhtar, H. (2000) · PubMed · Cited by 126 · see citing works
Nutrigenetics in Cancer Research—Folate Metabolism and Colorectal Cancer
Ulrich, C. M. (2005) · Journal of Nutrition · doi:10.1093/jn/135.11.2698 · Cited by 116 · see citing works
Targeting Ornithine Decarboxylase Impairs Development of MYCN -Amplified Neuroblastoma
Rounbehler, R. J., Li, W., Hall, M. A., Yang, C., Fallahi, M., & Cleveland, J. L. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2968 · Cited by 103 · 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
Histone 2B (H2B) Expression Is Confined to a Proper NAD+/NADH Redox Status
Dai, R.-P., Yu, F., Goh, S. R., Chng, H. W., Tan, Y.-L., Fu, J.-L., Zheng, L., & Luo, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804307200 · Cited by 81 · see citing works
MacFarlane, A. J., Perry, C. A., McEntee, M. F., Lin, D. M., & Stover, P. J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-1886 · Cited by 57 · see citing works
A Role for K-ras in Conferring Resistance to the MEK Inhibitor, CI-1040
Wangab, Y., Becelaere, K. V., Jiang, P., Przybranowski, S. A., Omer, C. A., & Sebolt, J. S. (2005) · Neoplasia · doi:10.1593/neo.04532 · Cited by 53 · see citing works
Zhong, X., & Howard, B. D. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.2.770 · Cited by 49 · see citing works
Höglund, A., Nilsson, L. M., Forshell, L. P., Maclean, K. H., & Nilsson, J. A. (2009) · Blood · doi:10.1182/blood-2008-10-183475 · Cited by 36 · see citing works
Self-citationA binding assay for serine hydroxymethyltransferase
Geller, A. M., & Kotb, M. Y. S. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90098-5 · Cited by 33 · see citing works
A Role for E2F Activities in Determining the Fate of Myc-Induced Lymphomagenesis
Rempel, R. E., Mori, S., Gasparetto, M., Glozak, M. A., Andrechek, E. R., Adler, S., Laakso, N., Lagoo, A. S., Storms, R. W., Smith, C., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000640 · Cited by 28 · see citing works
Pretsch, W., Merkle, S., Favor, J., & Werner, T. (1993) · Genetics · doi:10.1093/genetics/135.1.161 · Cited by 15 · see citing works
Self-citationLi, M., Ren, S., Tilli, M. T., Flaws, J. A., Lubet, R. A., Grubbs, C. J., & Furth, P. A. (2003) · Oncogene · doi:10.1038/sj.onc.1206314 · Cited by 8 · see citing works
Flagged first, then by citations
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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
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Targeting lactate metabolism for cancer therapeutics
Doherty, J. R., & Cleveland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69741 · Cited by 1,173 · see citing works
Serine and glycine metabolism in cancer
Amelio, I., Cutruzzolà, F., Antonov, A., Agostini, M., & Melino, G. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.004 · Cited by 1,056 · 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
Lieu, E. L., Nguyen, T. A., Rhyne, S., & Kim, J. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0375-3 · Cited by 827 · see citing works
MYC, Metabolism, Cell Growth, and TumorigenesisPreprint
Dang, C. V. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a014217 · Cited by 600 · see citing works
Xie, H., Hanai, J.-I., Ren, J.-G., Kats, L., Burgess, K., Bhargava, P., Signoretti, S., Billiard, J., Duffy, K. J., Grant, A., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.003 · Cited by 516 · see citing works
Metabolism of Amino Acids in Cancer
Wei, Z. C., Liu, X., Cheng, C., Yu, W., & Yi, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.603837 · Cited by 439 · see citing works
The importance of serine metabolism in cancer
Mattaini, K. R., Sullivan, M. R., & Heiden, M. G. V. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201604085 · Cited by 409 · see citing works
Regulation of cancer cell metabolism: Oncogenic MYC in the driver’s seat
Dong, Y., Tu, R., Liu, H., & Qing, G. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00235-2 · Cited by 405 · see citing works
The multiple roles of LDH in cancer
Claps, G., Faouzi, S., Quidville, V., Chehade, F., Shen, S., Vagner, S., & Robert, C. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00686-2 · Cited by 351 · see citing works
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 277 · see citing works
Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth
Krall, A. S., Mullen, P. J., Surjono, F., Momcilovic, M., Schmid, E. W., Halbrook, C. J., Thambundit, A., Mittelman, S. D., Lyssiotis, C. A., Shackelford, D. B., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.02.001 · Cited by 266 · see citing works
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 250 · see citing works
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 242 · see citing works
Bhadury, J., Nilsson, L. M., Muralidharan, S. V., Green, L. C., Li, Z., Gesner, E. M., Hansen, H. C., Keller, U. B., McLure, K. G., & Nilsson, J. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1406722111 · Cited by 215 · see citing works
Self-citationThe 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
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 198 · see citing works
Impact of MYC in regulation of tumor cell metabolism
Wahlström, T., & Arsenian‐Henriksson, M. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.07.004 · Cited by 176 · see citing works
Mitochondria, cholesterol and cancer cell metabolism
Ribas, V., García‐Ruiz, C., & Fernández-Checa, J. C. (2016) · Clinical and Translational Medicine · doi:10.1186/s40169-016-0106-5 · Cited by 159 · see citing works
The significant role of amino acid metabolic reprogramming in cancer
Liu, X., Ren, B., Ren, J., Gu, M., You, L., & Zhao, Y.-P. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01760-1 · Cited by 135 · see citing works
Reprogramming of serine, glycine and one-carbon metabolism in cancer
Li, A. M., & Ye, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165841 · Cited by 127 · see citing works
Liu, 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
Vučetić, M., Cormerais, Y., Parks, S. K., & Pouysségur, J. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00319 · Cited by 113 · see citing works
The Role of D-3-Phosphoglycerate Dehydrogenase in Cancer
Zhao, X., Fu, J., Du, J., & Xu, W. (2020) · International Journal of Biological Sciences · doi:10.7150/ijbs.41051 · Cited by 90 · see citing works
Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect
Wiese, E. K., & Hitosugi, T. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00079 · Cited by 82 · see citing works
Woo, C. C., Chen, W. C., Teo, X. Q., Radda, G. K., & Lee, P. T. H. (2016) · Oncotarget · doi:10.18632/oncotarget.10415 · Cited by 82 · see citing works
Dorneburg, C., Fischer, M., Barth, T. F. E., Mueller‐Klieser, W., Hero, B., Gecht, J., Carter, D. R., Preter, K. D., Mayer, B., Christner, L., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2578 · Cited by 81 · see citing works
Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers
Sun, W. Y., Liu, R., Gao, X., Lin, Z., Tang, H., Cui, H., & Zhao, E. (2023) · Biomarker Research · doi:10.1186/s40364-023-00487-4 · Cited by 82 · see citing works
Mutations in the Isocitrate Dehydrogenase Genes IDH1 and IDH2 in Tumors
Schaap, F. G., French, P. J., & Bovée, J. V. M. G. (2012) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e31827b654d · Cited by 78 · see citing works
Serine Biosynthesis Is a Metabolic Vulnerability in FLT3-ITD–Driven Acute Myeloid Leukemia
Bjelosevic, S., Gruber, E., Newbold, A., Shembrey, C., Devlin, J. R., Hogg, S. J., Kats, L. M., Todorovski, I., Fan, Z., Abrehart, T. C., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0738 · Cited by 77 · see citing works
Wang, C., Wan, X., Yu, T., Huang, Z., Shen, C., Qi, Q., Xiang, S., Chen, X., Arbely, E., Ling, Z.-Q., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108021 · Cited by 70 · see citing works
Gan, L., Xiu, R., Ren, P., Yue, M., Su, H., Guo, G., Xiao, D., Yu, J., Jiang, H., Liu, H., et al. (2015) · Oncogene · doi:10.1038/onc.2015.360 · Cited by 68 · see citing works
Autophagy, Warburg, and Warburg Reverse Effects in Human Cancer
González, C. D., Álvarez, S., Ropolo, A., Rosenzvit, C., Bagnes, M. F. G., & Vaccaro, M. I. (2014) · BioMed Research International · doi:10.1155/2014/926729 · Cited by 69 · see citing works
Determinants of nutrient limitation in cancer
Sullivan, M. R., & Heiden, M. G. V. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1611733 · Cited by 65 · see citing works
Han, X., Sheng, X., Jones, H. M., Jackson, A. L., Kilgore, J., Stine, J. E., Schointuch, M., Zhou, C., & Bae-Jump, V. L. (2015) · Journal of Hematology & Oncology · doi:10.1186/s13045-014-0097-x · Cited by 65 · see citing works
The PHGDH enigma: Do cancer cells only need serine or also a redox modulator?
Li, A. M., & Ye, J. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.01.036 · Cited by 65 · see citing works
Overview of Cancer Metabolism and Signaling Transduction
Chae, H., & Hong, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010012 · Cited by 63 · see citing works
MYC in Germinal Center‐derived lymphomas: Mechanisms and therapeutic opportunities
Bisso, A., Sabò, A., & Amati, B. B. (2019) · Immunological Reviews · doi:10.1111/imr.12734 · Cited by 48 · see citing works
Sim, W.-C., Lee, W., Sim, H., Lee, K.-Y., Jung, S.-H., Choi, Y., Kim, H., Kang, K. W., Lee, J.-Y., Choi, Y. J., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154000 · Cited by 51 · see citing works
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., Kluckova, K., Cheung, E. C., Clear, A. J., Gunawan, A. S., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci153436 · Cited by 47 · see citing works
Zhang, Y., Liu, Z., Wang, X., Jian, H., Xiao, H., & Wen, T. (2022) · Cancer Gene Therapy · doi:10.1038/s41417-022-00470-5 · Cited by 47 · see citing works
Pathogenesis and therapeutic targeting of aberrant MYC expression in haematological cancers
Schick, M., Habringer, S., Nilsson, J. A., & Keller, U. B. (2017) · British Journal of Haematology · doi:10.1111/bjh.14917 · Cited by 46 · see citing works
Self-citationMYC Oncogene: A Druggable Target for Treating Cancers with Natural Products
Chan, K. I., Zhang, S., Li, G., Xu, Y., Cui, L., Wang, Y., Su, H., Tan, W., & Zhong, Z. (2024) · Aging and Disease · doi:10.14336/ad.2023.0520 · Cited by 45 · see citing works
Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives
Yu, Z., Zhou, X., & Wang, X. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0917 · Cited by 42 · see citing works
Deiab, S., MAZZIO, E. A., Eyunni, S., McTier, O., Mateeva, N. N., Elshami, F. M., & Soliman, K. F. A. (2015) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2015/276946 · Cited by 39 · see citing works
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 39 · 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
Choi, B.-H., Rawat, V., Hogstrom, J. M., 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 36 · see citing works
O’Connor, S. T. F., Lan, J., North, M. R., Loguinov, A. V., Zhang, L., Smith, M. T., Gu, A. Z., & Vulpe, C. D. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2012.00316 · Cited by 38 · see citing works
Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer
Zhao, L., Deng, H., Zhang, J., Zamboni, N., Yang, H., Gao, Y., Zhang, Y., Xu, D., Zhong, H., van Geest, G., et al. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01427-x · Cited by 38 · see citing works
Warburg and Krebs and related effects in cancer
Unterlass, J. E., & Curtin, N. J. (2019) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2019.4 · Cited by 35 · see citing works
Nonsurgical embryo transfer device compared with surgery for embryo transfer in mice.
Steele, K. H., Hester, J., Stone, B. J., Carrico, K. M., Spear, B. T., & Fath‐Goodin, A. (2013) · Europe PMC (PubMed Central) · Cited by 33 · see citing works
Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence
Murali, R., Balasubramaniam, V., Srinivas, S., Sundaram, S., Venkatraman, G., Warrier, S. R., Dharmarajan, A., & Gandhirajan, R. K. (2023) · Metabolites · doi:10.3390/metabo13040560 · Cited by 32 · see citing works
High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors
Deiab, S. (2013) · European Journal of Medicinal Plants · doi:10.9734/ejmp/2013/5995 · Cited by 24 · see citing works
Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma
Pang, Y., Lu, T., Xu-Monette, Z. Y., & Young, K. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065493 · Cited by 25 · see citing works
Li, J., Yu, T., Xia, Z., Chen, G.-C., Yuan, Y., Zhong, W., Zhao, L., & Chen, Q. (2014) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2014.05.001 · Cited by 18 · see citing works
Li, Z., Zheng, W., Li, H., Li, C., & Gong, Z. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132319 · Cited by 17 · see citing works
Role of aerobic glycolysis in genetically engineered mouse models of cancer
Dang, C. V. (2013) · BMC Biology · doi:10.1186/1741-7007-11-3 · Cited by 15 · see citing works
N-Myc and L-Myc are essential for hair cell formation but not maintenance
Kopecky, B. J., DeCook, R. R., & Fritzsch, B. (2012) · Brain Research · doi:10.1016/j.brainres.2012.09.027 · Cited by 15 · see citing works
Metabolic Gatekeepers of Pathological B Cell Activation
Sadras, T., Chan, L. N., Xiao, G., & Müschen, M. (2020) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-061020-050135 · Cited by 14 · see citing works
Melanoma brain metastasis is independent of lactate dehydrogenase A expression
Sundstrøm, T., Espedal, H., Harter, P. N., Fasmer, K. E., Skaftnesmo, K. O., Horn, S. A., Hodneland, E., Mittelbronn, M. G. A., Weide, B., Beschorner, R., et al. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nov040 · Cited by 14 · see citing works
Increased PHGDH expression promotes aberrant melanin accumulation
Mattaini, K. R., Sullivan, M. R., Lau, A. N., Fiske, B. P., Bronson, R. T., & Heiden, M. G. V. (2019) · BMC Cancer · doi:10.1186/s12885-019-5933-5 · Cited by 13 · see citing works
Generation of c-Myc transgenic pigs for autosomal dominant polycystic kidney disease
Ye, J., He, J. H., Li, Q., Feng, Y., Bai, X., Chen, X., Zhao, Y., Hu, X., Yu, Z., & Li, N. (2013) · Transgenic Research · doi:10.1007/s11248-013-9707-6 · Cited by 9 · see citing works
Adiamah, M., Poole, B., Lindsey, J. C., Kohe, S. E., Morcavallo, A., Burté, F., Hill, R. M., Blair, H., Thompson, D., Singh, M., et al. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae179 · Cited by 8 · see citing works
Jiao, Z., Zhang, M., Ning, J., Yao, H., Yan, X., Wu, Z., Wu, D., Liu, Y., Zhang, M., Wang, L., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2412854122 · Cited by 8 · see citing works
Li, X., Han, B., Liu, D., Wang, S., Zhao, J., Wang, L., Li, R., Bao, G., Pei, Q., Sun, D., et al. (2025) · BMC Genomics · doi:10.1186/s12864-025-12098-4 · Cited by 7 · see citing works
Towards a metabolic therapy of cancer?
Chiu, M., Ottaviani, L., Bianchi, M. G., Franchi‐Gazzola, R., & Bussolati, O. (2012) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 7 · see citing works
Parkin on serine: a Parkinson disease gene suppresses serine synthesis in cancer
Dalton, W. B. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137411 · Cited by 7 · see citing works
Regulation of immune cell metabolism by cancer cell oncogenic mutations
Madi, A., & Cui, G. (2020) · International Journal of Cancer · doi:10.1002/ijc.32888 · Cited by 7 · see citing works
Mechanism and application of nonessential amino acid deprivation associated with tumor therapy
Nong, S., Qian, Y., Zhang, T., Zhou, X., Wei, Y., Yin, X., & Ma, X. (2022) · MedComm – Future Medicine · doi:10.1002/mef2.12 · Cited by 6 · see citing works
Control of epigenomic landscape and development of fetal male germ cells through L-serine metabolism
Hayashi, Y., Kaneko, J., Ito‐Matsuoka, Y., Takehara, A., Funakoshi, M., Maezawa, S., Shirane, K., Furuya, S., & Matsui, Y. (2024) · iScience · doi:10.1016/j.isci.2024.110702 · Cited by 5 · see citing works
Mitophagy and Reverse Warburg Effect: Metabolic Compartmentalization of Tumor Microenvironment
Naik, P. P. (2020) · Springer eBooks · doi:10.1007/978-981-15-6930-2_6 · Cited by 4 · see citing works
Modulating Autophagy and the “Reverse Warburg Effect”
Vaccaro, M. I., González, C. D., Álvarez, S., & Ropolo, A. (2014) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-1-4614-9545-1_6 · Cited by 4 · see citing works
Mitochondrial citrate transport represents a metabolic liability in MYCN-amplified neuroblastoma
Chen, C., Bao, Q., Huang, H., Wang, L., Jiang, J., Liu, H., Wang, Y., Qing, G., & Fang, Y. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2025.12.061 · Cited by 3 · see citing works
Genomic and Transcriptomic Approaches to Study Cancer in Small Aquarium Fish Models
Regneri, J., Klotz, B. J., & Schartl, M. (2016) · Advances in genetics · doi:10.1016/bs.adgen.2016.04.001 · Cited by 3 · see citing works
Quantification of the inputs and outputs of serine and glycine metabolism in cancer cells
Wang, Y., Wu, H., & Hu, X. (2025) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2025.110367 · Cited by 2 · see citing works
MYC Regulation of Metabolism and Cancer
Gouw, A. M., Hsieh, A. L., Stine, Z. E., & Dang, C. V. (2015) · Springer eBooks · doi:10.1007/978-3-7091-1824-5_5 · Cited by 2 · see citing works
Targeting Myc-driven tumours - BETing on ATR
Muralidharan, S. V. (2016) · Cited by 1 · see citing works
Mattaini, K. R., Sullivan, M. R., Lau, A. N., Fiske, B. P., Bronson, R. T., & Heiden, M. G. V. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/249250 · Cited by 1 · see citing works
Transient MYC Mimicking the Exercise Response Orchestrates Multifaceted Skeletal Muscle AdaptationsPreprint
Jones, R. G., Koopmans, P. J., Serrano, N., Cabrera, A. R., Morena, F., Chambers, T. L., Walters, R., Borowik, A., Taylor, M. E., Wohlgemuth, R. P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.29.735332 · Cited by 1 · see citing works
Using genetics to identify epigenetic and signal transduction targets in cancer
Bhadury, J. (2016) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Lung cancer and increase lactate dehydrogenases enzyme (LDH)
AL-Tai, T. H. H., & Al-Ammiri, H. H. (2026) · AIP conference proceedings · doi:10.1063/5.0321891
- Authors
- Nilsson, L. M., Plym Forshell, T. Z., Rimpi, S., Kreutzer, C., Pretsch, W., Bornkamm, G. W., & Nilsson, J. A.
- Affiliations
- University of Gothenburg (SE)
- Umeå University (SE)
- Helmholtz Munich (DE)
- Corresponding author
- Nilsson, Jonas A.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-03-15
- Volume
- 8
- Issue
- 3
- Pages
- e1002573
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3305401
- OpenAlex
- W2058552694
- Cited by
- 85
- References
- 62
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 2 · 2016: 8 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (University of Western Australia) (submittedVersion)
- DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Site cant be reached (submittedVersion, cc-by)
- Funders
- Cancerfonden
- Vetenskapsrådet
- Göteborgs Universitet
- Deutsche Krebshilfe
- RIKEN
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- c-Myc, carcinogenesis, metabolic enzymes, Warburg effect, glycolysis, LDHA, 3-phosphoglycerate dehydrogenase, synthetic lethality, oncogenic Ras, ApcMin/+ mice, p53 knockout mice, tumor metabolic adaptation
- MeSH terms
- Lactate Dehydrogenase 5, Animals, Cell Transformation, Neoplastic, Disease Models, Animal, Fibroblasts, Humans, Isoenzymes, L-Lactate Dehydrogenase, Mice, Inbred C57BL, Mice, Transgenic, Genes, ras, Glycine Hydroxymethyltransferase, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-myc, Lymphoma, B-Cell, Oligonucleotide Array Sequence Analysis, Adenomatous Polyposis Coli Protein, NIH 3T3 Cells, Phosphoglycerate Dehydrogenase, Mice, Metabolic Networks and Pathways
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