Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer
Open accessAbstract
Lactate accumulation in tumors has been associated with metastases and poor overall survival in cancer patients. Lactate promotes angiogenesis and metastasis, providing rationale for understanding how it is processed by cells. The concentration of lactate in tumors is a balance between the amount produced, amount carried away by vasculature and if/how it is catabolized by aerobic tumor or stromal cells. We examined lactate metabolism in human normal and breast tumor cell lines and rat breast cancer: 1. at relevant concentrations, 2. under aerobic vs. hypoxic conditions, 3. under conditions of normo vs. hypoglucosis. We also compared the avidity of tumors for lactate vs. glucose and identified key lactate catabolites to reveal how breast cancer cells process it. Lactate was non-toxic at clinically relevant concentrations. It was taken up and catabolized to alanine and glutamate by all cell lines. Kinetic uptake rates of lactate in vivo surpassed that of glucose in R3230Ac mammary carcinomas. The uptake appeared specific to aerobic tumor regions, consistent with the proposed "metabolic symbiont" model; here lactate produced by hypoxic cells is used by aerobic cells. We investigated whether treatment with alpha-cyano-4-hydroxycinnamate (CHC), a MCT1 inhibitor, would kill cells in the presence of high lactate. Both 0.1 mM and 5 mM CHC prevented lactate uptake in R3230Ac cells at lactate concentrations at ≤ 20 mM but not at 40 mM. 0.1 mM CHC was well-tolerated by R3230Ac and MCF7 cells, but 5 mM CHC killed both cell lines ± lactate, indicating off-target effects. This study showed that breast cancer cells tolerate and use lactate at clinically relevant concentrations in vitro (± glucose) and in vivo. We provided additional support for the metabolic symbiont model and discovered that breast cells prevailingly take up and catabolize lactate, providing rationale for future studies on manipulation of lactate catabolism pathways for therapy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Lactate produced in hypoxic regions of a tumor can fuel respiration in well-oxygenated tumor cells.
“It has been reported that lactate produced by cancer-associated fibroblasts can enter the TCA cycle of cancer cells (Bonuccelli et al., 2014; Witkiewicz et al., 2012), and lactate produced in hypoxic regions of a tumor can fuel respiration in well-oxygenated tumor cells (Kennedy et al., 2013; Sonveaux et al., 2008).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Kennedy et al., 2013
In cultured cells, pyruvate is largely produced from glucose via glycolysis; in vivo, circulating lactate provides an additional major source of tissue pyruvate.
“In cultured cells, pyruvate is largely produced from glucose via glycolysis; in vivo, circulating lactate provides an additional major source of tissue pyruvate (46, 47, 48).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784 · see citing works
Robbins and Cotran Pathologic Basis of Disease
Hoda, S. A., & Hoda, R. S. (2020) · American Journal of Clinical Pathology · doi:10.1093/ajcp/aqaa163 · Cited by 3,369 · see citing works
A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes
Neve, R. M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F. L., Fevr, T., Clark, L., Bayani, N., Coppé, J., Tong, F. K., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.008 · Cited by 3,191 · see citing works
Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy
Rouzier, R., Perou, C. M., Symmans, W. F., Ibrahim, N. K., Cristofanilli, M., Anderson, K., Hess, K. R., Stec, J. J., Ayers, M., Wagner, P., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2421 · Cited by 1,889 · see citing works
Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
Sonveaux, P., Végran, F., Schroeder, T., Wergin, M., Verrax, J., Rabbani, Z. N., Saedeleer, C. J. D., Kennedy, K. M., Diepart, C., Jordan, B. F., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36843 · Cited by 1,635 · see citing works
Self-citationThe reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma
Pavlides, S., Whitaker-Menezes, D., Castello-Cros, R., Flomenberg, N., Witkiewicz, A. K., Frank, P. G., Casimiro, M. C., Wang, C., Fortina, P., Addya, S., et al. (2009) · Cell Cycle · doi:10.4161/cc.8.23.10238 · Cited by 1,391 · see citing works
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation
Halestrap, A. P., & Price, N. T. (1999) · Biochemical Journal · doi:10.1042/bj3430281 · Cited by 1,346 · see citing works
Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells.
Reitzer, L. J., Wice, B. M., & Kennell, D. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30124-2 · Cited by 1,240 · see citing works
(1996) · PubMed · Cited by 1,188 · see citing works
Oncogenic alterations of metabolism
Dang, C. V., & Semenza, G. L. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01344-9 · Cited by 1,106 · see citing works
Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck
Brizel, D. M., Sibley, G. S., Prosnitz, L. R., Scher, R. L., & Dewhirst, M. W. (1997) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(97)00101-6 · Cited by 1,068 · see citing works
Self-citationHalestrap, A. P., & Meredith, D. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1067-2 · Cited by 1,047 · see citing works
Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock*
Mikkelsen, M. E., Miltiades, A., Gaieski, D. F., Goyal, M. K., Fuchs, B. D., Shah, C. V., Bellamy, S. L., & Christie, J. D. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e31819fcf68 · Cited by 1,002 · see citing works
Tumor microenvironmental physiology and its implications for radiation oncology
Vaupel, P. W. (2004) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2004.04.008 · Cited by 948 · see citing works
Ullah, M. S., Davies, A. J., & Halestrap, A. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511397200 · Cited by 894 · see citing works
Walenta, S., Wetterling, M., Lehrke, M., Schwickert, G., Sundfør, K., Rofstad, E. K., & Mueller‐Klieser, W. (2000) · PubMed · Cited by 817 · see citing works
WARBURN, O., & Dickens, F. (1931) · The American Journal of the Medical Sciences · doi:10.1097/00000441-193107000-00022 · Cited by 813 · see citing works
Alanine: Key Role in Gluconeogenesis
Felig, P., Pozefsk, T., Marlis, E., & Cahill, G. F. (1970) · Science · doi:10.1126/science.167.3920.1003 · Cited by 596 · see citing works
Brizel, D. M., Schroeder, T., Scher, R. L., Walenta, S., Clough, R. W., Dewhirst, M. W., & Mueller‐Klieser, W. (2001) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(01)01630-3 · Cited by 587 · see citing works
Self-citationDIMMER, K.-S., Friedrich, B., Lang, F. J. W., Deitmer, J. W., & Bröer, S. (2000) · Biochemical Journal · doi:10.1042/bj3500219 · Cited by 579 · see citing works
The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors
Halestrap, A. P. (1975) · Biochemical Journal · doi:10.1042/bj1480085 · Cited by 543 · see citing works
Sonveaux, P., Copetti, T., De Saedeleer, C. J., Végran, F., Verrax, J., Kennedy, K. M., Moon, E. J., Dhup, S., Danhier, P., Frérart, F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033418 · Cited by 536 · see citing works
Self-citationLactate: mirror and motor of tumor malignancy
Walenta, S., & Mueller‐Klieser, W. (2004) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2004.04.004 · Cited by 432 · see citing works
Anticancer Targets in the Glycolytic Metabolism of Tumors: A Comprehensive Review
Porporato, P. E., Dhup, S., Dadhich, R. K., Copetti, T., & Sonveaux, P. (2011) · Frontiers in Pharmacology · doi:10.3389/fphar.2011.00049 · Cited by 424 · see citing works
Self-citationDhup, S., Dadhich, R. K., Porporato, P. E., & Sonveaux, P. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799504902 · Cited by 419 · see citing works
Self-citationGuillaumond, F., Leca, J., Olivares, O., Lavaut, M.-N., Vidal, N., Berthezène, P., Dusetti, N. J., Loncle, C., Calvo, E., Turrini, O., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219555110 · Cited by 413 · see citing works
Favaro, E., Bensaad, K., Chong, M., Tennant, D. A., Ferguson, D. J. P., Snell, C. E., Steers, G., Turley, H., Li, J., Günther, U. L., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.017 · Cited by 389 · see citing works
Maddocks, O. D. K., & Vousden, K. H. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0735-5 · Cited by 359 · see citing works
Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer
Gatenby, R. A., Smallbone, K., Maini, P. K., et al. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603922 · Cited by 343 · see citing works
Spitz, D. R., Sim, J. E., Ridnour, L. A., Galoforo, S., & Lee, Y. J. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06199.x · Cited by 331 · see citing works
Fox, J. E. M., Meredith, D., & Halestrap, A. P. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00285.x · Cited by 331 · see citing works
Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation
Kennedy, K. M., & Dewhirst, M. (2010) · Future Oncology · doi:10.2217/fon.09.145 · Cited by 317 · see citing works
Self-citationPavlides, S., Vera, I., Gândara, R., Sneddon, S., Pestell, R. G., Mercier, I., Martinez‐Outschoorn, U., Whitaker‐Menezes, D., Howell, A., Sotgia, F., et al. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4243 · Cited by 289 · see citing works
Lactate Activates HIF-1 in Oxidative but Not in Warburg-Phenotype Human Tumor Cells
Saedeleer, C. J. D., Copetti, T., Porporato, P. E., Verrax, J., Féron, O., & Sonveaux, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046571 · Cited by 274 · see citing works
Self-citationIncreased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas
Pinheiro, C. M., Longatto‐Filho, A., Scapulatempo‐Neto, C., Ferreira, L., Martins, S. F. F., Pellerin, L., Rodrigues, M., Alves, V. A. F., Schmitt, F. C., & Baltazar, F. (2008) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-007-0558-5 · Cited by 254 · see citing works
Correlation of high lactate levels in head and neck tumors with incidence of metastasis.
Walenta, S., Salameh, A., Lyng, H., Evensen, J. F., Mitze, M., Rofstad, E. K., & Mueller‐Klieser, W. (1997) · Europe PMC (PubMed Central) · Cited by 251 · see citing works
Mitochondrial O2⋅¯ and H2O2 Mediate Glucose Deprivation-induced Stress in Human Cancer Cells
Ahmad, I. M., Aykin‐Burns, N., Sim, J. E., Walsh, S. A., Higashikubo, R., Buettner, G. R., Venkataraman, S., Mackey, M. A., Flanagan, S. W., Oberley, L. W., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411662200 · Cited by 246 · see citing works
Walenta, S., Schroeder, T. V., & Mueller‐Klieser, W. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043364711 · Cited by 246 · see citing works
Self-citationMCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors
Birsoy, K., Wang, T., Possemato, R., Yilmaz, Ö. H., Koch, C. E., Chen, W. W., Hutchins, A., Gültekin, Y., Peterson, T. R., Carette, J. E., et al. (2012) · Nature Genetics · doi:10.1038/ng.2471 · Cited by 226 · see citing works
Correlation of high lactate levels in human cervical cancer with incidence of metastasis.
Schwickert, G., Walenta, S., Sundfør, K., Rofstad, E. K., & Mueller-Klieser, W. (1995) · PubMed · Cited by 225 · see citing works
Bonuccelli, G., Whitaker‐Menezes, D., Castelló-Cros, R., Pavlides, S., Pestell, R. G., Fatatis, A., Witkiewicz, A. K., Heiden, M. G. V., Migneco, G., Chiavarina, B., et al. (2010) · Cell Cycle · doi:10.4161/cc.9.10.11601 · Cited by 223 · see citing works
Boidot, R., Végran, F., Meulle, A., Breton, A. L., Dessy, C., Sonveaux, P., Lizard‐Nacol, S., & Féron, O. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-2474 · Cited by 221 · see citing works
Self-citationHui, L., Zheng, Y., Yan, Y., Bargonetti, J., & Foster, D. A. (2006) · Oncogene · doi:10.1038/sj.onc.1209735 · Cited by 218 · see citing works
The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers
Chen, J. L.-Y., Lucas, J. E., Schroeder, T., Mori, S., Wu, J., Nevins, J. R., Dewhirst, M. W., West, M., & Chi, J. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000293 · Cited by 214 · see citing works
Self-citationMonocarboxylate transporter 1 is up‐regulated in basal‐like breast carcinoma
Pinheiro, C. M., Albergaria, A., Paredes, J., Sousa, B., Dufloth, R. M., Vieira, D. S. C., Schmitt, F. C., & Baltazar, F. (2010) · Histopathology · doi:10.1111/j.1365-2559.2010.03560.x · Cited by 188 · see citing works
Hussien, R., & Brooks, G. A. (2010) · Physiological Genomics · doi:10.1152/physiolgenomics.00177.2010 · Cited by 176 · see citing works
Pinheiro, C. M., Reis, R. M., Ricardo, S. A. V., Longatto‐Filho, A., Schmitt, F. C., & Baltazar, F. (2010) · BioMed Research International · doi:10.1155/2010/427694 · Cited by 171 · see citing works
Fang, J., Quiñones, Q. J., Holman, T. L., Morowitz, M. J., Wang, Q., Zhao, H., Sivo, F., Maris, J. M., & Wahl, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.026245 · Cited by 171 · see citing works
Hilf, R., Murant, R. S., Narayanan, U., et al. (1986) · PubMed · Cited by 162 · see citing works
Blackburn, R. V., Spitz, D. R., Liu, X. Z., Galoforo, S., Sim, J. E., Ridnour, L. A., Chen, J. C., Davis, B. H., Corry, P. M., & Lee, Y. J. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00217-2 · Cited by 158 · see citing works
Pavlides, S., Tsirigos, A., Vera, I., Flomenberg, N., Frank, P. G., Casimiro, M. C., Wang, C., Pestell, R. G., Martinez‐Outschoorn, U., Howell, A., et al. (2010) · Aging · doi:10.18632/aging.100134 · Cited by 151 · see citing works
Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath tumors
Kourea, H. P., Bilsky, M. H., Leung, D. H. Y., Lewis, J. J., & Woodruff, J. M. (1998) · Cancer · doi:10.1002/(sici)1097-0142(19980601)82:11 · Cited by 149 · see citing works
Marín‐Hernández, Á., Gallardo‐Pérez, J. C., Rodríguez‐Enríquez, S., Encalada, R., Moreno‐Sánchez, R., & Saavedra, E. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.11.006 · Cited by 146 · see citing works
Diers, A. R., Broniowska, K. A., Chang, C.-F., & Hogg, N. (2012) · Biochemical Journal · doi:10.1042/bj20120294 · Cited by 133 · see citing works
Lactate: A major product of glutamine metabolism by human diploid fibroblasts
Zielke, H. R., Sumbilla, C. M., Sevdalian, D. A., Hawkins, R. L., & Ozand, P. T. (1980) · Journal of Cellular Physiology · doi:10.1002/jcp.1041040316 · Cited by 123 · see citing works
Schroeder, T., Yuan, H., Viglianti, B. L., Peltz, C. D., Asopa, S., Vujašković, Ž., & Dewhirst, M. W. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3900 · Cited by 118 · see citing works
Self-citationKatayose, D., Gudas, J. M., Nguyen, H., Srivastava, S., Cowan, K. H., & Seth, P. K. (1995) · PubMed · Cited by 106 · see citing works
Walenta, S., Chau, T.-V., Schroeder, T., Lehr, H., Kunz‐Schughart, L. A., Fuerst, A., & Mueller‐Klieser, W. (2003) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-003-0450-x · Cited by 106 · see citing works
Self-citationGlucose deprivation-induced metabolic oxidative stress and cancer therapy
Spitz, D. R., Simons, A. L., Mattson, D., & Dornfeld, K. J. (2009) · Journal of Cancer Research and Therapeutics · doi:10.4103/0973-1482.55133 · Cited by 106 · see citing works
Abundance and subcellular distribution of MCT1 and MCT4 in heart and fast-twitch skeletal muscles
Bonen, A., Miskovic, D., Tonouchi, M., Lemieux, K., Wilson, M. C., Marette, A., & Halestrap, A. P. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.278.6.e1067 · Cited by 106 · see citing works
Pinheiro, C. M., Longatto‐Filho, A., Ferreira, L., Pereira, S. M. M., Etlinger, D., Moreira, M. A. R., Jubé, L. F., Queiroz, G. S., Schmitt, F. C., & Baltazar, F. (2008) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0b013e31817b5b40 · Cited by 102 · see citing works
Mueller-Klieser, W., & Walenta, S. (1993) · The Histochemical Journal · doi:10.1007/bf00157805 · Cited by 93 · see citing works
Manning, J. E., Katz, L. M., Brownstein, M. R., et al. (2000) · Shock · doi:10.1097/00024382-200013020-00010 · Cited by 83 · see citing works
Cerebrospinal fluid lactate in 78 cases of adult meningitis
Genton, B., & Berger, J. P. (1990) · Intensive Care Medicine · doi:10.1007/bf01724802 · Cited by 81 · see citing works
Reduced Expression of GNA11 and Silencing of MCT1 in Human Breast Cancers
Asada, K., Miyamoto, K., Fukutomi, T., Tsuda, H., Yagi, Y., Wakazono, K., Oishi, S., Fukui, H., Sügimura, T., & Ushijima, T. (2003) · Oncology · doi:10.1159/000070297 · Cited by 73 · see citing works
Walenta, S., Snyder, S. A., Haroon, Z. A., Braun, R. D., Amin, K., Brizel, D. M., Mueller‐Klieser, W., Chance, B., & Dewhirst, M. W. (2001) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(01)01700-x · Cited by 69 · see citing works
Self-citationYokota, H., Guo, J., Matoba, M., et al. (2007) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.20902 · Cited by 66 · see citing works
Bouzier‐Sore, A., Voisin, P. J., Goodwin, R., et al. (1998) · Developmental Neuroscience · doi:10.1159/000017328 · Cited by 63 · see citing works
Kim, H. S., Masko, E. M., Poulton, S. L., et al. (2012) · British Journal of Urology · doi:10.1111/j.1464-410x.2012.10971.x · Cited by 47 · see citing works
Komarova, E. A., Zelnick, C. R., Chin, D., Zeremski, M., Gleiberman, A. S., Bacus, S. S., & Gudkov, A. V. (1997) · PubMed · Cited by 45 · see citing works
L-3-11C-Lactate as a PET Tracer of Myocardial Lactate Metabolism: A Feasibility Study
Herrero, P., Dence, C. S., Coggan, A. R., Kisrieva-Ware, Z., Eisenbeis, P. E., & Gropler, R. J. (2007) · Journal of Nuclear Medicine · doi:10.2967/jnumed.107.044503 · Cited by 42 · see citing works
Ibrahim, E. M., Al-Gahmi, A., Zeeneldin, A. A., et al. (2008) · Medical Oncology · doi:10.1007/s12032-008-9131-6 · Cited by 35 · see citing works
Lactate MRSI and DCE MRI as surrogate markers of prostate tumor aggressiveness
Yaligar, J., Thakur, S. B., Bokacheva, L., Carlin, S., Thaler, H. T., Rizwan, A., Lupu, M. E., Wang, Y., Matei, C., Zakian, K. L., et al. (2011) · NMR in Biomedicine · doi:10.1002/nbm.1723 · Cited by 25 · see citing works
α-Cyano-4-hydroxycinnamate induces apoptosis in Dalton’s lymphoma cells
Kumar, A., Kant, S., & Singh, S. M. (2012) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e3283586743 · Cited by 20 · see citing works
In vivo lactate production and utilization by Jensen sarcoma and Morris hepatoma 7288CTC.
Sauer, L. A., & Dauchy, R. T. (1986) · PubMed · Cited by 17 · see citing works
Effect of exogenous lactate on rat glioma metabolism
Bouzier‐Sore, A., Canioni, P., & Merle, M. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.1184 · Cited by 16 · see citing works
5: Laboratory Reference Range Values
(2019) · American Academy of Pediatrics eBooks · doi:10.1542/9781610022811-ch05 · Cited by 14 · see citing works
Sauer, L. A., & Dauchy, R. T. (1994) · Metabolism · doi:10.1016/0026-0495(94)90006-x · Cited by 12 · see citing works
Mapping and quantification of biomolecules in tumor biopsies using bioluminescence
Schwickert, G., Walenta, S., & Mueller-Klieser, W. (1996) · Cellular and Molecular Life Sciences · doi:10.1007/bf01919316 · Cited by 6 · see citing works
Peltz, C. D., Schroeder, T., & Dewhirst, M. W. (2006) · Springer eBooks · doi:10.1007/0-387-26206-7_45 · Cited by 5 · see citing works
Self-citationOs, F., & Stoika, R. S. (2006) · PubMed · Cited by 4 · see citing works
The Effect of Nicotinamide & Hyperoxic Gases on Blood Glucose
Richardson, R. A., & Dewhirst, M. W. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0205-0_62 · Cited by 2 · see citing works
Self-citationGlycogen accumulation in cultured tumoral or normal pancreatic islet and acinar cells
Rasschaert, J., & Malaisse, W. J. (2001) · International Journal of Molecular Medicine · doi:10.3892/ijmm.8.1.63 · Cited by 1 · see citing works
The effect of toremifene on the expression of genes in a rat mammary adenocarcinoma.
Kellen, J. A., & Mirakian, A. (1997) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [5]Warburg OH, Kaiser-Wilhelm-Institut fuÎr Biologie. (1926) Ãœber den Stoffwechsel der Tumoren: Arbeiten aus dem Kaiser Wilheim-Institut für Biologie, Berlin-Dahlem. Berlin: Julius Springer.263 p. p.
- [62]Halestrap AP (2008) Inhibiting lactate oxidation in tumor cells. eLetters: The Journal of Clinical Investigation.
Cited by
Sorted by citations
Glucose feeds the TCA cycle via circulating lactate
Hui, S., Ghergurovich, J. M., Morscher, R. J., Jang, C., Teng, X., Lu, W., Esparza, L. A., Reya, T., Zhan, L., Yanxiang Guo, J., et al. (2017) · Nature · doi:10.1038/nature24057 · Cited by 1,721 · see citing works
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505 · see citing works
Lactate Metabolism in Human Lung Tumors
Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.019 · Cited by 1,343 · see citing works
Metabolic heterogeneity in human lung tumors
Hensley, C. T., Faubert, B., Yuan, Q., Lev-Cohain, N., Jin, E., Kim, J., Jiang, L., Ko, B., Skelton, R., Loudat, L., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.034 · Cited by 1,138 · see citing works
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches
de la Cruz-López, K. G., Castro-Muñoz, L. J., Reyes-Hernández, D. O., García-Carrancá, A., & Manzo-Merino, J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01143 · Cited by 940 · see citing works
Metabolic Interactions in the Tumor Microenvironment
Lyssiotis, C. A., & Kimmelman, A. C. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.003 · Cited by 853 · see citing works
Increased demand for NAD(+) relative to ATP drives aerobic glycolysis
Luengo, A., Li, Z., Gui, D. Y., Sullivan, L. B., Zagorulya, M., Do, B. T., Ferreira, R., Naamati, A., Ali, A., Lewis, C. A., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.012 · Cited by 547 · see citing works
Regulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535 · see citing works
Courtney, K. D., Bezwada, D., Mashimo, T., Pichumani, K., Vemireddy, V., Funk, A. M., Wimberly, J., McNeil, S. S., Kapur, P., Lotan, Y., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.020 · Cited by 280 · see citing works
Lactate promotes glutamine uptake and metabolism in oxidative cancer cells
Pérez-Escuredo, J., Dadhich, R. K., Dhup, S., Cacace, A., Van Hée, V. F., De Saedeleer, C. J., Sboarina, M., Rodriguez, F., Fontenille, M.-J., Brisson, L., et al. (2016) · Cell Cycle · doi:10.1080/15384101.2015.1120930 · Cited by 231 · see citing works
Self-citationAllen, E., Miéville, P., Warren, C. M., Saghafinia, S., Li, L., Peng, M.-W., & Hanahan, D. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.029 · Cited by 221 · see citing works
Obre, E., & Rossignol, R. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.12.008 · Cited by 137 · see citing works
Alternative fuels for cancer cells
Keenan, M. M., & Chi, J.-T. (2015) · The Cancer Journal · doi:10.1097/ppo.0000000000000104 · Cited by 131 · see citing works
Self-citation
- Authors
- Kennedy, K. M., Scarbrough, P. M., Ribeiro, A., Richardson, R., Yuan, H., Sonveaux, P., Landon, C. D., Chi, J.-T., Pizzo, S., Schroeder, T., & Dewhirst, M. W.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- University of North Carolina at Chapel Hill (US)
- UCLouvain (BE)
- Corresponding author
- Kennedy, Kelly M.
- Scarbrough, Peter M.
- Ribeiro, Anthony
- Richardson, Rachel
- Yuan, Hong
- Sonveaux, Pierre
- Landon, Chelsea D.
- Chi, Jen-Tsan
- Pizzo, Salvatore
- Schroeder, Thies
- Dewhirst, Mark W.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-12
- Volume
- 8
- Issue
- 9
- Pages
- e75154
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3771963
- OpenAlex
- W2024007253
- Cited by
- 190
- References
- 85
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 9 · 2023: 9 · 2022: 15 · 2021: 25 · 2020: 17 · 2019: 22 · 2018: 15 · 2017: 18 · 2016: 19 · 2015: 11 · 2014: 6
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- UNC Libraries
- Funders
- U.S. Department of Defense
- National Institutes of Health (CA40355, NCI CA40355)
- U.S. Public Health Service (243188 TUMETABO)
- National Cancer Institute (CA40355, BC083154, R01CA125618, R01CA040355, T32CA078586)
- FP7 Ideas: European Research Council (243188)
- 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 › Molecular Biology › Cancer and biochemical research
- Keywords
- breast cancer, lactate metabolism, lactate utilization, alanine, glutamate, MCT1 inhibition, HCCA, tumor hypoxia, MCF-7 cells
- MeSH terms
- Adult, Aged, Alanine, Animals, Breast Neoplasms, Coumaric Acids, Disease Models, Animal, Female, Glucose, Humans, Kinetics, Middle Aged, Neoplasm Staging, Cell Hypoxia, Cell Death, Glutamic Acid, Lactic Acid, Cell Line, Tumor, Rats, Metabolic Networks and Pathways, Metabolomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
