Targeting aspartate aminotransferase in breast cancer
Open accessAbstract
Introduction: Glycolysis is increased in breast adenocarcinoma cells relative to adjacent normal cells in order to produce the ATP and anabolic precursors required for survival, growth and invasion. Glycolysis also serves as a key source of the reduced form of cytoplasmic nicotinamide adenine dinucleotide (NADH) necessary for the shuttling of electrons into mitochondria for electron transport. Lactate dehydrogenase (LDH) regulates glycolytic flux by converting pyruvate to lactate and has been found to be highly expressed in breast tumours. Aspartate aminotransferase (AAT) functions in tandem with malate dehydrogenase to transfer electrons from NADH across the inner mitochondrial membrane. Oxamate is an inhibitor of both LDH and AAT, and we hypothesised that oxamate may disrupt the metabolism and growth of breast adenocarcinoma cells. Methods: We examined the effects of oxamate and the AAT inhibitor amino oxyacetate (AOA) on 13 C-glucose utilisation, oxygen consumption, NADH and ATP in MDA-MB-231 cells. We then determined the effects of oxamate and AOA on normal human mammary epithelial cells and MDA-MB-231 breast adenocarcinoma cell proliferation, and on the growth of MDA-MB-231 cells as tumours in athymic BALB/c female mice. We ectopically expressed AAT in MDA-MB-231 cells and examined the consequences on the cytostatic effects of oxamate. Finally, we examined the effect of AAT-specific siRNA transfection on MDA-MB-231 cell proliferation. Results: We found that oxamate did not attenuate cellular lactate production as predicted by its LDH inhibitory activity, but did have an anti-metabolic effect that was similar to AAT inhibition with AOA. Specifically, we found that oxamate and AOA decreased the flux of 13 C-glucose-derived carbons into glutamate and uridine, both products of the mitochondrial tricarboxylic acid cycle, as well as oxygen consumption, a measure of electron transport chain activity. Oxamate and AOA also selectively suppressed the proliferation of MDA-MB-231 cells relative to normal human mammary epithelial cells and decreased the growth of MDA-MB-231 breast tumours in athymic mice. Importantly, we found that ectopic expression of AAT in MDA-MB-231 cells conferred resistance to the anti-proliferative effects of oxamate and that siRNA silencing of AAT decreased MDA-MB-231 cell proliferation. Conclusions: We conclude that AAT may be a valid molecular target for the development of anti-neoplastic agents.
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Glutamate consumption by aminotransferases to generate NEAAs is required for tumor growth in diverse cancer types.
“Glutamate consumption by aminotransferases to generate NEAAs has also been indicated to be required for tumor growth in diverse cancer types29,40–42.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [40]
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Cites
Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892 · see citing works
Markert, C. L., Shaklee, J. B., & Whitt, G. S. (1975) · Science · doi:10.1126/science.1138367 · Cited by 566 · see citing works
Avril, N. E., Menzel, M. M., Dose, J., Schelling, M., Weber, W., Jänicke, F., NATHRATH, W. B. J., & Schwaiger, M. (2001) · PubMed · Cited by 412 · see citing works
Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements
Ramanathan, A., Wang, C., & Schreiber, S. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502267102 · Cited by 357 · see citing works
McKenna, M. C., Waagepetersen, H. S., Schousboe, A., & Sonnewald, U. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.10.011 · Cited by 328 · see citing works
C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance
Deming, S. L., Nass, S. J., Dickson, R. B., & Trock, B. J. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1522 · Cited by 302 · see citing works
Metabolic Fate of 14C‐Labeled Glutamate in Astrocytes in Primary Cultures
Yu, A., Schousboec, A., & Hertz, L. (1982) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1982.tb11482.x · Cited by 292 · see citing works
Gallagher, S. M., Castorino, J. J., Wang, D., & Philp, N. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3184 · Cited by 289 · see citing works
Craniopharyngiomas. A clinical and pathological review
Petito, C. K., Girolami, U. D., & Earle, K. M. (1976) · Cancer · doi:10.1002/1097-0142(197604)37:4 · Cited by 265 · see citing works
Ford, G. C., Eichele, G., & Jansonius, J. N. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.5.2559 · Cited by 240 · see citing works
Initiating oncogenic event determines gene-expression patterns of human breast cancer models
Desai, K. V., Xiao, N., Wang, W., Gangi, L., Greene, J. P., Powell, J. I., Dickson, R. B., Furth, P. A., Hunter, K. W., Kucherlapati, R., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102172399 · Cited by 196 · see citing works
Crystal Structures of Escherichia coli Aspartate Aminotransferase in Two Conformations
Jäger, J., Moser, M., Sauder, U., & Jansonius, J. N. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1368 · Cited by 188 · see citing works
Ras transformation requires metabolic control by 6-phosphofructo-2-kinase
Telang, S., Yalçın, A., Clem, A. L., Bucala, R., Lane, A. N., Eaton, J. W., & Chesney, J. A. (2006) · Oncogene · doi:10.1038/sj.onc.1209709 · Cited by 166 · see citing works
Self-citationOkamoto, A., Higuchi, T., Hirotsu, K., Kuramitsu, S., & Kagamiyama, H. (1994) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a124509 · Cited by 149 · see citing works
Fitzpatrick, S. M., Cooper, A. J. L., & Duffy, T. E. (1983) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1983.tb00835.x · Cited by 113 · see citing works
The Role of Glycolysis in the Growth of Tumor Cells
Papaconstantinou, J., & Colowick, S. P. (1961) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64352-2 · Cited by 110 · see citing works
Yu, A. C.-H., Schousboe, A., & Hertz, L. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb02721.x · Cited by 104 · see citing works
Occurrence of the malate-aspartate shuttle in various tumor types.
Greenhouse, W. V. V., & Lehninger, A. L. (1976) · PubMed · Cited by 99 · see citing works
Wu, G., Aoyama, C., Young, S. G., & Vance, D. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708766200 · Cited by 99 · see citing works
Tumor induction by the c-Myc target genes rcl and lactate dehydrogenase A.
Lewis, B. C., Prescott, J. E., Campbell, S. E., Shim, H., Orlowski, R. Z., & Dang, C. V. (2000) · PubMed · Cited by 98 · see citing works
Smith, D. L., Almo, S. C., Toney, M. D., & Ringe, D. (1989) · Biochemistry · doi:10.1021/bi00446a030 · Cited by 92 · see citing works
Choline Kinase Down-regulation Increases the Effect of 5-Fluorouracil in Breast Cancer Cells
Mori, N., Glunde, K., Takagi, T., Raman, V., & Bhujwalla, Z. M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2728 · Cited by 82 · see citing works
Characterization of shuttle mechanisms for the transport of reducing equivalents into mitochondria
Cederbaum, A. I., Lieber, C. S., Beattie, D. S., & Rubin, E. (1973) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(73)90571-7 · Cited by 78 · see citing works
Bos, R., van Diest, P. J., van der Groep, P., Shvarts, A., Greijer, A. E., & van der Wall, E. (2004) · Breast Cancer Research · doi:10.1186/bcr813 · Cited by 77 · see citing works
Isozyme patterns of normal, benign, and malignant human breast tissues.
Balinsky, D., Platz, C. E., & Lewis, J. (1983) · PubMed · Cited by 72 · see citing works
Kamitori, S., Okamoto, A., Hirotsu, K., Higuchi, T., Kuraxnitsu, S., Kagamiyama, H., Matsuura, Y., & Katsube, Y. (1990) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a123178 · Cited by 67 · see citing works
Differential Expression and Mutation of therasFamily Genes in Human Breast Cancer
Miyakis, S., Sourvinos, G., & Spandidos, D. A. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9527 · Cited by 65 · see citing works
Targeted disruption of inducible 6-phosphofructo-2-kinase results in embryonic lethality
Chesney, J. A., Telang, S., Yalçın, A., Clem, A. L., Wallis, N. K., & Bucala, R. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.02.193 · Cited by 64 · see citing works
Self-citationThe Role of Glycolysis in the Growth of Tumor Cells
Papaconstantinou, J., & Colowick, S. P. (1961) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64353-4 · Cited by 63 · see citing works
The H-ras oncogene product p21 and prognosis in human breast cancer
Watson, D. M., Elton, R. A., Jack, W. J. L., Dixon, J. M., Chetty, U., & Miller, W. R. (1991) · Breast Cancer Research and Treatment · doi:10.1007/bf01806365 · Cited by 57 · see citing works
The Role of Glycolysis in the Growth of Tumor Cells
Goldberg, E. B., Nitowsky, H. M., & Colowick, S. P. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97248-0 · Cited by 55 · see citing works
Taetle, R., Rosen, F. S., ABRAMSON, I. S., Venditti, J. M., & Howell, S. B. (1987) · PubMed · Cited by 46 · see citing works
Three-dimensional structure at 5 Å resolution of cytosolic aspartate transaminase from chicken heart
Borisov, V. V., Borisova, S. N., Качалова, Г. С., Sosfenov, N. I., Vainshtein, B. K., Torchinsky, Y. M., & Braunstein, A. (1978) · Journal of Molecular Biology · doi:10.1016/0022-2836(78)90403-5 · Cited by 44 · see citing works
The Role of Glycolysis in the Growth of Tumor Cells
Goldberg, E. B., & Colowick, S. P. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97247-9 · Cited by 36 · see citing works
Crystal structure of Saccharomyces cerevisiae cytosolic aspartate aminotransferase
Jeffery, C. J., Petsko, G. A., Ringe, D., Barry, T. N., & Doonan, S. (1998) · Protein Science · doi:10.1002/pro.5560070614 · Cited by 31 · see citing works
Oxamate as a Differential Inhibitor of Lactate Dehydrogenase Isoenzymes
Wilkinson, J. H., & Walter, S. J. (1972) · Enzyme · doi:10.1159/000459658 · Cited by 25 · see citing works
Chiaretti, B., Casciaro, A., Minotti, G., Eboli, M. L., & Galeotti, T. (1979) · PubMed · Cited by 21 · see citing works
p21 ras protein expression in benign and malignant
Walker, R. A., & Wilkinson, N. S. (1988) · The Journal of Pathology · doi:10.1002/path.1711560209 · Cited by 21 · see citing works
Measurement of aspartate aminotransferase activity: effects of oxamate.
Rej, R. (1979) · Clinical Chemistry · doi:10.1093/clinchem/25.4.555 · Cited by 20 · see citing works
López‐Alarcón, L., & Eboli, M. L. (1986) · PubMed · Cited by 19 · see citing works
Expression of ras oncogene p21 protein in relation to regional spread of human breast carcinomas
Czerniak, B. A., Chen, R., Tuziak, T., Markiewski, M. M., Kram, A., Gorczyca, W., Deitch, D., Herz, F., & Koss, L. G. (1989) · Cancer · doi:10.1002/1097-0142(19890515)63:10 · Cited by 18 · see citing works
Estrogen control of lactate dehydrogenase isoenzyme‐5 in human breast cancer
Nagai, M. A., Sonohara, S., & Brintani, M. M. (1988) · International Journal of Cancer · doi:10.1002/ijc.2910410104 · Cited by 14 · see citing works
Arai, T., Ogawa, T., Nakamura, M., Hosoya, M., & Ohnishi, Y. (2002) · Journal of Veterinary Medical Science · doi:10.1292/jvms.64.1065 · Cited by 8 · see citing works
Nagy, I., Hirka, G., Kurcz, M., Anda, E., & Baranyai, P. (1978) · PubMed · Cited by 8 · see citing works
[X-ray-structural study of aspartate transaminase at 5 A resolution].
Borisov, V. V., Sn, B., Gs, K., Sosfenov, N. I., & Aa, V. (1977) · PubMed · Cited by 6 · see citing works
Crystallographic and chemical studies on cytosolic aspartate aminotransferase.
Arnone, A., Rogers, P. H., Hyde, C. C., Makinen, M. W., Feldhaus, R., Metzler, C. M., & De, M. (1984) · PubMed · Cited by 4 · see citing works
BRAUNSHTEIN, A. E., Arutyunyan, E. G., Malashkevich, V. N., Kochkina, V. M., & Torchinskiĭ, I. M. (1985) · PubMed · Cited by 3 · see citing works
Flagged first, then by citations
2 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Voet D Voet J Metabolism: Glycolysis. Biochemistry 1995 Second Wiley and Sons, USA 444 476
- Cooper AJL Meister A Transaminases 1985 New York: John Wiley and Sons
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Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427 · see citing works
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997 · see citing works
Glutamine addiction: a new therapeutic target in cancer
Wise, D. R., & Thompson, C. B. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.003 · Cited by 1,770 · see citing works
Targeting mitochondria metabolism for cancer therapy
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Glutamine and cancer: cell biology, physiology, and clinical opportunities
Hensley, C. T., Wasti, A. T., & DeBerardinis, R. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69600 · Cited by 1,262 · see citing works
Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021 · see citing works
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Regulation of mammalian nucleotide metabolism and biosynthesis
Lane, A. N., & Fan, T. W.-M. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv047 · Cited by 959 · see citing works
Self-citationSzabó, C., Coletta, C., Chao, C., Módis, K., Szczęsny, B., Papapetropoulos, A., & Hellmich, M. R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1306241110 · Cited by 768 · see citing works
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Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017) · The EMBO Journal · doi:10.15252/embj.201696151 · Cited by 651 · see citing works
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Yang, Y., Karakhanova, S., Hartwig, W., D’Haese, J. G., Philippov, P. P., Werner, J., & Bazhin, A. V. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25349 · Cited by 671 · see citing works
San-Millán, I., & Brooks, G. A. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw127 · Cited by 612 · see citing works
Timmerman, L. A., Holton, T., Yuneva, M., Louie, R. J., Padró, M., Daemen, A., Hu, M., Chan, D. A., Ethier, S. P., van ‘t Veer, L. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.08.020 · Cited by 573 · see citing works
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Ferguson, B. S., Rogatzki, M. J., Goodwin, M. L., Kane, D. A., Rightmire, Z. B., & Gladden, L. B. (2018) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3795-6 · Cited by 451 · see citing works
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Xiang, Y., Stine, Z. E., Xia, J., Lu, Y., O’Connor, R. S., Altman, B. J., Hsieh, A. L., Gouw, A. M., Thomas, A. G., Gao, P., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci75836 · Cited by 409 · see citing works
Cao, X., Ding, L., Xie, Z., Yang, Y., Whiteman, M., Moore, P. K., & Bian, J. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7058 · Cited by 409 · see citing works
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Zhou, M., Zhao, Y., Ding, Y., Liu, H., Liu, Z., Fodstad, Ø., Riker, A. I., Kamarajugadda, S., Lu, J., Owen, L. B., et al. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-33 · Cited by 395 · see citing works
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Hao, Y., Samuels, Y., Li, Q., Krokowski, D., Guan, B.-J., Wang, C., Jin, Z., Dong, B., Cao, B., Feng, X., et al. (2016) · Nature Communications · doi:10.1038/ncomms11971 · Cited by 290 · see citing works
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Sheng, S. L., Liu, J., Dai, Y., Sun, X. G., Xiong, X. P., & Huang, G. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08748.x · Cited by 263 · see citing works
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Yang, H., Zhou, L., Shi, Q., Zhao, Y., Lin, H., Zhang, M., Zhao, S., Yang, Y. A., Ling, Z., Guan, K., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201591041 · Cited by 224 · see citing works
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Módis, K., Bos, E. M., Calzia, E., van Goor, H., Coletta, C., Papapetropoulos, A., Hellmich, M. R., Radermacher, P., Bouillaud, F., & Szabó, C. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12368 · Cited by 163 · see citing works
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Lee, W., Ji, X., Nissim, I., & Long, F. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108108 · Cited by 143 · see citing works
Small mitochondria-targeting molecules as anti-cancer agents
Wang, F., Ogasawara, M. A., & Huang, P. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.12.003 · Cited by 143 · see citing works
Synergistic Anti-Cancer Effect of Phenformin and Oxamate
Miskimins, W. K., Ahn, H. J., Kim, J. Y., Ryu, S., Jung, Y., & Choi, J. Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085576 · Cited by 144 · see citing works
Sormendi, S., & Wielockx, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00040 · Cited by 141 · see citing works
Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy
Dong, L., Gopalan, V., Holland, O. J., & Neužil, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217941 · Cited by 135 · see citing works
Altered energy metabolism in cancer: A unique opportunity for therapeutic intervention
Zhang, Y., & Yang, J.-M. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.22958 · Cited by 132 · see citing works
Metabolic alterations in cancer cells and therapeutic implications
Hammoudi, N., Ahmed, K. B. R., Garcı́a-Prieto, C., & Huang, P. (2011) · 癌症：英文版 · doi:10.5732/cjc.011.10267 · Cited by 134 · see citing works
Isocitrate dehydrogenases in physiology and cancer: biochemical and molecular insight
Al‐Khallaf, H. (2017) · Cell & Bioscience · doi:10.1186/s13578-017-0165-3 · Cited by 127 · see citing works
Cystathionineβ-Synthase in Physiology and Cancer
Zhu, H., Blake, S., Chan, K. T., Pearson, R. B., & Kang, J. (2018) · BioMed Research International · doi:10.1155/2018/3205125 · Cited by 123 · see citing works
Glutamine Metabolism in Cancer
Li, T., Copeland, C., & Le, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-65768-0_2 · Cited by 130 · see citing works
Stable isotope resolved metabolomics of lung cancer in a SCID mouse model
Fan, T. W. ‐., Lane, A. N., Higashi, R. M., & Yan, J. (2010) · Metabolomics · doi:10.1007/s11306-010-0249-0 · Cited by 115 · see citing works
Self-citationGlutamine‐fueled mitochondrial metabolism is decoupled from glycolysis in melanoma
Filipp, F. V., Ratnikov, B. I., Ingeniis, J. D., Smith, J. W., Osterman, A. L., & Scott, D. A. (2012) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12000 · Cited by 107 · see citing works
Hassouni, B. E., Granchi, C., Vallés‐Martí, A., Supadmanaba, I. G. P., Bononi, G., Tuccinardi, T., Funel, N., Jiménez, C. R., Peters, G. J., Giovannetti, E., et al. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.025 · Cited by 110 · see citing works
Emerging roles of cystathionine β-synthase in various forms of cancer
Ascenção, K., & Szabó, C. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102331 · Cited by 105 · see citing works
O’Neal, J., Clem, A. L., Reynolds, L., Dougherty, S. M., Imbert-Fernandez, Y., Telang, S., Chesney, J. A., & Clem, B. F. (2016) · Breast Cancer Research and Treatment · doi:10.1007/s10549-016-3968-8 · Cited by 105 · see citing works
Self-citationSmall-Molecule Inhibitors of Human Ldh5
Granchi, C., Paterni, I., Rani, R., & Minutolo, F. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.151 · Cited by 99 · see citing works
Enzyme Tunnels and Gates As Relevant Targets in Drug Design
Marques, S. M., Daniel, L., Buryška, T., Prokop, Z., Brezovský, J., & Damborský, J. (2016) · Medicinal Research Reviews · doi:10.1002/med.21430 · Cited by 98 · see citing works
Drug resistance induces the upregulation of H2S-producing enzymes in HCT116 colon cancer cells
Untereiner, A. A., Pavlidou, A., Druzhyna, N., Papapetropoulos, A., Hellmich, M. R., & Szabó, C. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.10.007 · Cited by 98 · see citing works
Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling
Yalçın, A., Clem, B. F., Makoni, S. N., Clem, A. L., Nelson, K. K., Thornburg, J. M., Siow, D. L., Lane, A. N., Brock, S. E., Goswami, U., et al. (2009) · Oncogene · doi:10.1038/onc.2009.317 · Cited by 97 · see citing works
Self-citationNon-viral nanocarriers for siRNA delivery in breast cancer
Zhang, J., Li, X., & Huang, L. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.05.037 · Cited by 96 · see citing works
Ocaña, M. C., Martı́nez-Poveda, B., Quesada, A. R., & Medina, M. Á. (2018) · Medicinal Research Reviews · doi:10.1002/med.21511 · Cited by 91 · see citing works
Lu, Q., Zhang, L., Yee, J. K., Go, V. W., & Lee, W. P. (2014) · Metabolomics · doi:10.1007/s11306-014-0672-8 · Cited by 88 · see citing works
Lane, A. N., Fan, T. W. ‐., Bousamra, M., Higashi, R. M., Yan, J., & Miller, D. M. (2011) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2010.0088 · Cited by 87 · see citing works
Self-citationLactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy
Hao, Z.-N., Tan, X.-P., Zhang, Q., Li, J., Xia, R., & Ma, Z. (2024) · Biomolecules · doi:10.3390/biom14121646 · Cited by 87 · see citing works
Nilsson, L. M., Plym Forshell, T. Z., Rimpi, S., Kreutzer, C., Pretsch, W., Bornkamm, G. W., & Nilsson, J. A. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002573 · Cited by 85 · see citing works
Glutamate and asparagine cataplerosis underlie glutamine addiction in melanoma
Ratnikov, B. I., Aza‐Blanc, P., Ronai, Z. A., Smith, J. W., Osterman, A. L., & Scott, D. A. (2015) · Oncotarget · doi:10.18632/oncotarget.3132 · Cited by 80 · see citing works
The Ephrin-A1/EPHA2 Signaling Axis Regulates Glutamine Metabolism in HER2-Positive Breast Cancer
Youngblood, V., Kim, L. C., Edwards, D. N., Hwang, Y., Santapuram, P. R., Stirdivant, S. M., Lu, P., Ye, F., Brantley‐Sieders, D. M., & Chen, J. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-0847 · Cited by 81 · see citing works
Chao, C., Zatarain, J. R., Ding, Y., Coletta, C., Mrazek, A. A., Druzhyna, N., Johnson, P. R., Chen, H., Hellmich, J. L., Asimakopoulou, A., et al. (2016) · Molecular Medicine · doi:10.2119/molmed.2016.00102 · Cited by 74 · see citing works
AST/ALT ratio as a significant predictor of the incidence risk of prostate cancer
Zhou, J., He, Z., Ma, S., & Liu, R. (2020) · Cancer Medicine · doi:10.1002/cam4.3086 · Cited by 72 · see citing works
ATP citrate lyase is increased in human breast cancer, depletion of which promotes apoptosis
Wang, D., Yin, L., Wei, J., Yang, Z.-X., & Jiang, G. (2017) · Tumor Biology · doi:10.1177/1010428317698338 · Cited by 68 · see citing works
Saqcena, M., Mukhopadhyay, S., Hosny, C., Alhamed, A., Chatterjee, A., & Foster, D. A. (2015) · Oncogene · doi:10.1038/onc.2014.207 · Cited by 67 · see citing works
Lee, H., Lee, S. E., Byun, S., Kim, H. H., Kwak, C. H., & Hong, S. K. (2016) · British Journal of Urology · doi:10.1111/bju.13545 · Cited by 66 · see citing works
Metabolic changes in triple negative breast cancer-focus on aerobic glycolysis
Arundhathi, J. R. D., Mathur, S. R., Gogia, A., Deo, S. V. S., Mohapatra, P., & Prasad, C. P. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06414-w · Cited by 65 · see citing works
Cancer cell metabolism: Rewiring the mitochondrial hub
Oliveira, G. L., Coelho, A. R., Marques, R., & Oliveira, P. J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166016 · Cited by 62 · see citing works
Yang, W. S., Moon, H., Kim, H. S., Choi, E., Yu, M., Noh, D., & Lee, C. (2011) · Journal of Proteome Research · doi:10.1021/pr2008187 · Cited by 64 · see citing works
Metabolic changes in cancer cells upon suppression of MYC
Ansó, E., Mullen, A. R., Felsher, D. W., Matés, J. M., DeBerardinis, R. J., & Chandel, N. S. (2013) · Cancer & Metabolism · doi:10.1186/2049-3002-1-7 · Cited by 61 · see citing works
Bioenergetic Metabolism In Osteoblast Differentiation
Shen, L., Hu, G., & Karner, C. M. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00721-2 · Cited by 61 · see citing works
Wang, H., Fang, K., Zhang, J., Jiang, Y., Wang, G., Zhang, H., Chen, T., Shi, X., Li, Y., Duan, F., et al. (2017) · International Urology and Nephrology · doi:10.1007/s11255-017-1618-7 · Cited by 61 · see citing works
Matschke, J., Riffkin, H., Klein, D., Handrick, R., Lüdemann, L., Metzen, E., Shlomi, T., Stuschke, M., & Jendrossek, V. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6589 · Cited by 60 · see citing works
From cancer metabolism to new biomarkers and drug targets
Chiaradonna, F., Moresco, R. M., Airoldi, C., Gaglio, D., Palorini, R., Nicotra, F., Messa, C., & Alberghina, L. (2011) · Biotechnology Advances · doi:10.1016/j.biotechadv.2011.07.006 · Cited by 59 · see citing works
Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered
Kinlaw, W. B., Baures, P. W., Lupien, L. E., Davis, W. L., & Kuemmerle, N. B. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25332 · Cited by 57 · see citing works
Sun, W., Luan, S., Qi, C., Tong, Q., Yan, S., Li, H., & Zhang, Y. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0425-4 · Cited by 59 · see citing works
Battini, S., Faitot, F., Impériale, A., Çiçek, A. E., Heimburger, C., Avérous, G., Bachellier, P., & Namer, I. J. (2017) · BMC Medicine · doi:10.1186/s12916-017-0810-z · Cited by 57 · see citing works
Dual Targeting of the Warburg Effect with a Glucose‐Conjugated Lactate Dehydrogenase Inhibitor
Calvaresi, E. C., Granchi, C., Tuccinardi, T., Bussolo, V. D., Huigens, R. W., Lee, H. Y., Palchaudhuri, R., Macchia, M., Martinelli, A., Minutolo, F., et al. (2013) · ChemBioChem · doi:10.1002/cbic.201300562 · Cited by 56 · see citing works
Oberkersch, R. E., Pontarin, G., Astone, M., Spizzotin, M., Arslanbaeva, L. R., Tosi, G., Panieri, E., Ricciardi, S., Allega, M. F., Brossa, A., et al. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.04.018 · Cited by 55 · see citing works
Lowered circulating aspartate is a metabolic feature of human breast cancer
Xie, G., Zhou, B., Zhao, A., Qiu, Y., Zhao, X., Garmire, L. X., Shvetsov, Y. B., Yu, H., Yen, Y., & Jia, W. P. (2015) · Oncotarget · doi:10.18632/oncotarget.5409 · Cited by 55 · see citing works
Hwang, J. S., Kim, S. G., Shin, T. H., Jang, Y. E., Kwon, D. H., & Lee, G. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14050997 · Cited by 54 · see citing works
Wang, C., Chen, H., Zhang, M., Zhang, J., Wei, X., & Ying, W. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.05.001 · Cited by 54 · see citing works
Cell death-based treatment of neuroblastoma
Valter, K., Zhivotovsky, B., & Gogvadze, V. G. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0060-1 · Cited by 52 · see citing works
Wu, J., Chen, L., Wang, Y., Tan, W., & Huang, Z. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s204403 · Cited by 51 · see citing works
Mitochondrial Metabolism Inhibitors for Cancer Therapy
Ramsay, E. E., Hogg, P. J., & Dilda, P. J. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0584-5 · Cited by 51 · see citing works
Specific Inhibition of the Aspartate Aminotransferase of Plasmodium falciparum
Wrenger, C., Müller, I. B., Schifferdecker, A. J., Jain, R., Jordanova, R., & Groves, M. R. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.11.018 · Cited by 51 · see citing works
- Authors
- Thornburg, J. M., Nelson, K. K., Clem, B. F., Lane, A. N., Arumugam, S., Simmons, A., Eaton, J. W., Telang, S., & Chesney, J.
- Affiliations
- University of Louisville (US)
- Corresponding author
- Chesney, Jason
- Venue
- Breast Cancer Research
- Published
- 2008-10-15
- Volume
- 10
- Issue
- 5
- Pages
- R84-R84
- ISSN
- 1465-5411 (ISSN-L)
- 1465-542X
- PMC
- PMC2614520
- OpenAlex
- W2107254151
- Cited by
- 288
- References
- 49
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 16 · 2023: 16 · 2022: 24 · 2021: 19 · 2020: 26 · 2019: 26 · 2018: 20 · 2017: 16 · 2016: 24 · 2015: 20 · 2014: 17 · 2013: 16 · 2012: 8
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Breast Cancer Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca116428-02)
- National Cancer Institute (R01CA116428, 1 R01 CA116428-01)
- 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 › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- aspartate aminotransferase, breast cancer, oxamate, aminooxyacetic acid, glycolysis, mitochondrial electron transport chain, NADH, lactate dehydrogenase, malate dehydrogenase, TCA cycle, glutamate, uridine, oxygen consumption, MDA-MB-231 cells
- MeSH terms
- Lactate Dehydrogenase 5, Adenocarcinoma, Aminooxyacetic Acid, Animals, Antineoplastic Agents, Aspartate Aminotransferases, Breast Neoplasms, Cell Division, Citric Acid Cycle, Female, Glycolysis, Humans, Isoenzymes, L-Lactate Dehydrogenase, Mice, Inbred BALB C, Mice, Nude, Neoplasm Proteins, Oxamic Acid, Recombinant Fusion Proteins, Tumor Stem Cell Assay, Drug Delivery Systems, Xenograft Model Antitumor Assays, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Mice, Cytostatic Agents
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