Monocarboxylate Transporter 1 in Brain Diseases and Cancers

Yixin       Sun; Jin       Sun; Zhonggui       He; Gang       Wang; Yang       Wang; Dongyang       Zhao; Zhenjie       Wang; Cong       Luo; Chutong       Tian; Qikun       Jiang
Abstract

Background: Monocarboxylate Transporter 1 (MCT1), an important membrane transport protein, mediates the translocation of monocarboxylates together with protons across biological membranes. Due to its pathological significance, MCT1 plays an important role in the progression of some diseases, such as brain diseases and cancers.
Methods: We summarize the general description of MCT1 and provide a comprehensive understanding of the role of MCT1 in brain diseases and cancers. Furthermore, this review discusses the opportunities and challenges of MCT1- targeting drug-delivery systems in the treatment of brain diseases and cancers.
Results: In the brain, loss of MCT1 function is associated with pathologies of degeneration and injury of the nervous system. In tumors, MCT1 regulates the activity of signaling pathways and controls the exchange of monocarboxylates in aerobic glycolysis to affect tumor metabolism, proliferation and invasion. Meanwhile, MCT1 also acts as a good biomarker for the prediction and diagnosis of cancer progressions.
Conclusion: MCT1 is an attractive transporter in brain diseases and cancers. Moreover, the development of MCT1- based small molecule drugs and MCT1 inhibitors in the clinic is promising. This review systematically summarizes the basic characteristics of MCT1 and its role in brain diseases and cancers, laying the foundation for further research on MCT1.
Keywords: Monocarboxylate transporter 1, cancer, brain diseases, drug-delivery, lactate, MCT1 inhibitors.
Graphical Abstract

[1] 
Halestrap, A.P.; Meredith, D. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch.,  2004, 447(5), 619-628.
[http://dx.doi.org/10.1007/s00424-003-1067-2] [PMID:  12739169] 
[2] 
Pérez-Escuredo, J.; Van Hée, V.F.; Sboarina, M.; Falces, J.; Payen, V.L.; Pellerin, L.; Sonveaux, P. Monocarboxylate transporters in the brain and in cancer. Biochim. Biophys. Acta,  2016, 1863(10), 2481-2497.
[http://dx.doi.org/10.1016/j.bbamcr.2016.03.013] [PMID:  26993058] 
[3] 
Guo, C.; Huang, T.; Wang, Q.H.; Li, H.; Khanal, A.; Kang, E.H.; Zhang, W.; Niu, H.T.; Dong, Z.; Cao, Y.W. Monocarboxylate transporter 1 and monocarboxylate transporter 4 in cancer-endothelial co-culturing microenvironments promote proliferation, migration, and invasion of renal cancer cells. Cancer Cell Int.,  2019, 19, 170.
[http://dx.doi.org/10.1186/s12935-019-0889-8] [PMID:  31297034] 
[4] 
Jha, M.K.; Lee, Y.; Russell, K.A.; Yang, F.; Dastgheyb, R.M.; Deme, P.; Ament, X.H.; Chen, W.; Liu, Y.; Guan, Y.; Polydefkis, M.J.; Hoke, A.; Haughey, N.J.; Rothstein, J.D.; Morrison, B.M. Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging. Glia,  2020, 68(1), 161-177.
[http://dx.doi.org/10.1002/glia.23710] [PMID:  31453649] 
[5] 
Zhou, P.; Guan, T.; Jiang, Z.; Namaka, M.; Huang, Q.J.; Kong, J.M. Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage cells to metabolic stresses. CNS Neurosci. Ther.,  2018, 24(2), 126-134.
[http://dx.doi.org/10.1111/cns.12782] [PMID:  29205833] 
[6] 
Jeon, J.Y.; Lee, M.; Whang, S.H.; Kim, J.W.; Cho, A.; Yun, M. Regulation of acetate utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC). Oncol. Res.,  2018, 26(1), 71-81.
[http://dx.doi.org/10.3727/096504017X14902648894463] [PMID:  28390113] 
[7] 
Pierre, K.; Pellerin, L. Monocarboxylate transporters in the central nervous system: Distribution, regulation and function. J. Neurochem.,  2005, 94(1), 1-14.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03168.x] [PMID:  15953344] 
[8] 
Fünfschilling, U.; Supplie, L.M.; Mahad, D.; Boretius, S.; Saab, A.S.; Edgar, J.; Brinkmann, B.G.; Kassmann, C.M.; Tzvetanova, I.D.; Möbius, W.; Diaz, F.; Meijer, D.; Suter, U.; Hamprecht, B.; Sereda, M.W.; Moraes, C.T.; Frahm, J.; Goebbels, S.; Nave, K.A. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature,  2012, 485(7399), 517-521.
[http://dx.doi.org/10.1038/nature11007] [PMID:  22622581] 
[9] 
Amaral, A.I.; Meisingset, T.W.; Kotter, M.R.; Sonnewald, U. Metabolic aspects of neuron-oligodendrocyte-astrocyte interactions. Front. Endocrinol. (Lausanne),  2013, 4, 54.
[http://dx.doi.org/10.3389/fendo.2013.00054] [PMID:  23717302] 
[10] 
Zhang, M.; Ma, Z.; Qin, H.; Yao, Z. Monocarboxylate transporter 1 in the medial prefrontal cortex developmentally expresses in oligodendrocytes and associates with neuronal amounts. Mol. Neurobiol.,  2017, 54(3), 2315-2326.
[http://dx.doi.org/10.1007/s12035-016-9820-7] [PMID:  26957300] 
[11] 
Medin, T.; Medin, H.; Hefte, M.B.; Storm-Mathisen, J.; Bergersen, L.H. Upregulation of the lactate transporter monocarboxylate transporter 1 at the blood-brain barrier in a rat model of attention-deficit/hyperactivity disorder suggests hyperactivity could be a form of self-treatment. Behav. Brain Res.,  2019, 360, 279-285.
[http://dx.doi.org/10.1016/j.bbr.2018.12.023] [PMID:  30550949] 
[12] 
Cardone, R.A.; Casavola, V.; Reshkin, S.J. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat. Rev. Cancer,  2005, 5(10), 786-795.
[http://dx.doi.org/10.1038/nrc1713] [PMID:  16175178] 
[13] 
Le, A.; Cooper, C.R.; Gouw, A.M.; Dinavahi, R.; Maitra, A.; Deck, L.M.; Royer, R.E.; Vander Jagt, D.L.; Semenza, G.L.; Dang, C.V. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc. Natl. Acad. Sci. USA,  2010, 107(5), 2037-2042.
[http://dx.doi.org/10.1073/pnas.0914433107] [PMID:  20133848] 
[14] 
Polański, R.; Hodgkinson, C.L.; Fusi, A.; Nonaka, D.; Priest, L.; Kelly, P.; Trapani, F.; Bishop, P.W.; White, A.; Critchlow, S.E.; Smith, P.D.; Blackhall, F.; Dive, C.; Morrow, C.J. Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer. Clin. Cancer Res.,  2014, 20(4), 926-937.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2270] [PMID:  24277449] 
[15] 
Berginc, K.; Kristl, A. The mechanisms responsible for garlic-drug interactions and their in vivo relevance. Curr. Drug Metab.,  2013, 14(1), 90-101.
[http://dx.doi.org/10.2174/138920013804545188] [PMID:  21838705] 
[16] 
Latif, A.; Chadwick, A.L.; Kitson, S.J.; Gregson, H.J.; Sivalingam, V.N.; Bolton, J.; McVey, R.J.; Roberts, S.A.; Marshall, K.M.; Williams, K.J.; Stratford, I.J.; Crosbie, E.J.; Williams, K.J.; Stratford, I.J.; Crosbie, E.J. Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer. BMC Clin. Pathol.,  2017, 17, 27.
[http://dx.doi.org/10.1186/s12907-017-0067-7] [PMID:  29299023] 
[17] 
Halestrap, A.P. The SLC16 gene family-structure, role and regulation in health and disease. Mol. Aspects Med.,  2013, 34(2-3), 337-349.
[http://dx.doi.org/10.1016/j.mam.2012.05.003] [PMID:  23506875] 
[18] 
Manoharan, C.; Wilson, M.C.; Sessions, R.B.; Halestrap, A.P. The role of charged residues in the transmembrane helices of monocarboxylate transporter 1 and its ancillary protein basigin in determining plasma membrane expression and catalytic activity. Mol. Membr. Biol.,  2006, 23(6), 486-498.
[http://dx.doi.org/10.1080/09687860600841967] [PMID:  17127621] 
[19] 
Wilson, M.C.; Meredith, D.; Bunnun, C.; Sessions, R.B.; Halestrap, A.P. Studies on the DIDS-binding site of monocarboxylate transporter 1 suggest a homology model of the open conformation and a plausible translocation cycle. J. Biol. Chem.,  2009, 284(30), 20011-20021.
[http://dx.doi.org/10.1074/jbc.M109.014217] [PMID:  19473976] 
[20] 
Galić, S.; Schneider, H.P.; Bröer, A.; Deitmer, J.W.; Bröer, S. The loop between helix 4 and helix 5 in the monocarboxylate transporter MCT1 is important for substrate selection and protein stability. Biochem. J.,  2003, 376(Pt 2), 413-422.
[http://dx.doi.org/10.1042/bj20030799] [PMID:  12946269] 
[21] 
Halestrap, A.P.; Wilson, M.C. The monocarboxylate transporter family-role and regulation. IUBMB Life,  2012, 64(2), 109-119.
[http://dx.doi.org/10.1002/iub.572] [PMID:  22162139] 
[22] 
Bonen, A. The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. Eur. J. Appl. Physiol.,  2001, 86(1), 6-11.
[http://dx.doi.org/10.1007/s004210100516] [PMID:  11820324] 
[23] 
Kroemer, G.; Pouyssegur, J. Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell,  2008, 13(6), 472-482.
[http://dx.doi.org/10.1016/j.ccr.2008.05.005] [PMID:  18538731] 
[24] 
Murray, C.M.; Hutchinson, R.; Bantick, J.R.; Belfield, G.P.; Benjamin, A.D.; Brazma, D.; Bundick, R.V.; Cook, I.D.; Craggs, R.I.; Edwards, S.; Evans, L.R.; Harrison, R.; Holness, E.; Jackson, A.P.; Jackson, C.G.; Kingston, L.P.; Perry, M.W.D.; Ross, A.R.J.; Rugman, P.A.; Sidhu, S.S.; Sullivan, M.; Taylor-Fishwick, D.A.; Walker, P.C.; Whitehead, Y.M.; Wilkinson, D.J.; Wright, A.; Donald, D.K. Monocarboxylate transporter MCT1 is a target for immunosuppression. Nat. Chem. Biol.,  2005, 1(7), 371-376.
[http://dx.doi.org/10.1038/nchembio744] [PMID:  16370372] 
[25] 
Benton, C.R.; Yoshida, Y.; Lally, J.; Han, X.X.; Hatta, H.; Bonen, A. PGC-1alpha increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiol. Genomics,  2008, 35(1), 45-54.
[http://dx.doi.org/10.1152/physiolgenomics.90217.2008] [PMID:  18523157] 
[26] 
Boidot, R.; Végran, F.; Meulle, A.; Le Breton, A.; Dessy, C.; Sonveaux, P.; Lizard-Nacol, S.; Feron, O. Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors. Cancer Res.,  2012, 72(4), 939-948.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-2474] [PMID:  22184616] 
[27] 
El Hayek, L.; Khalifeh, M.; Zibara, V.; Abi Assaad, R.; Emmanuel, N.; Karnib, N.; El-Ghandour, R.; Nasrallah, P.; Bilen, M.; Ibrahim, P.; Younes, J.; Abou Haidar, E.; Barmo, N.; Jabre, V.; Stephan, J.S.; Sleiman, S.F. Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal Brain-Derived Neurotrophic Factor (BDNF). J. Neurosci.,  2019, 39(13), 2369-2382.
[http://dx.doi.org/10.1523/JNEUROSCI.1661-18.2019] [PMID:  30692222] 
[28] 
Martins, I.J. Nutrition therapy regulates caffeine metabolism with relevance to NAFLD and induction of type 3 diabetes. J. Diabetes Metab. Disord.,  2017, 4(1), 1-9.
[29] 
Martins, I.J. Single gene inactivation with implications to diabetes and multiple organ dysfunction syndrome. J. Clin. Epigenet.,  2017, 3(3), 24.
[http://dx.doi.org/10.21767/2472-1158.100058] 
[30] 
Vaziri, H.; Dessain, S.K.; Ng Eaton, E.; Imai, S.I.; Frye, R.A.; Pandita, T.K.; Guarente, L.; Weinberg, R.A. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell,  2001, 107(2), 149-159.
[http://dx.doi.org/10.1016/S0092-8674(01)00527-X] [PMID:  11672523] 
[31] 
Wang, X.; Michael, D.; de Murcia, G.; Oren, M. p53 Activation by nitric oxide involves down-regulation of Mdm2. J. Biol. Chem.,  2002, 277(18), 15697-15702.
[http://dx.doi.org/10.1074/jbc.M112068200] [PMID:  11867628] 
[32] 
Macdonald, P.M. Translational control: A cup half full. Curr. Biol.,  2004, 14(7), R282-R283.
[http://dx.doi.org/10.1016/j.cub.2004.03.025] [PMID:  15062123] 
[33] 
Jóhannsson, E.; Lunde, P.K.; Heddle, C.; Sjaastad, I.; Thomas, M.J.; Bergersen, L.; Halestrap, A.P.; Blackstad, T.W.; Ottersen, O.P.; Sejersted, O.M. Upregulation of the cardiac monocarboxylate transporter MCT1 in a rat model of congestive heart failure. Circulation,  2001, 104(6), 729-734.
[http://dx.doi.org/10.1161/hc3201.092286] [PMID:  11489783] 
[34] 
Halestrap, A.P.; Price, N.T. The proton-linked Monocarboxylate Transporter (MCT) family: structure, function and regulation. Biochem. J.,  1999, 343(Pt 2), 281-299.
[http://dx.doi.org/10.1042/bj3430281] [PMID:  10510291] 
[35] 
Bola, B.M.; Chadwick, A.L.; Michopoulos, F.; Blount, K.G.; Telfer, B.A.; Williams, K.J.; Smith, P.D.; Critchlow, S.E.; Stratford, I.J. Inhibition of Monocarboxylate Transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport. Mol. Cancer Ther.,  2014, 13(12), 2805-2816.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-1091] [PMID:  25281618] 
[36] 
Ovens, M.J.; Davies, A.J.; Wilson, M.C.; Murray, C.M.; Halestrap, A.P. AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10. Biochem. J.,  2010, 425(3), 523-530.
[http://dx.doi.org/10.1042/BJ20091515] [PMID:  19929853] 
[37] 
Doherty, J.R.; Yang, C.; Scott, K.E.; Cameron, M.D.; Fallahi, M.; Li, W.; Hall, M.A.; Amelio, A.L.; Mishra, J.K.; Li, F.; Tortosa, M.; Genau, H.M.; Rounbehler, R.J.; Lu, Y.; Dang, C.V.; Kumar, K.G.; Butler, A.A.; Bannister, T.D.; Hooper, A.T.; Unsal-Kacmaz, K.; Roush, W.R.; Cleveland, J.L. Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis. Cancer Res.,  2014, 74(3), 908-920.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2034] [PMID:  24285728] 
[38] 
Ekberg, H.; Qi, Z.; Pahlman, C.; Veress, B.; Bundick, R.V.; Craggs, R.I.; Holness, E.; Edwards, S.; Murray, C.M.; Ferguson, D.; Kerry, P.J.; Wilson, E.; Donald, D.K. The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat. Transplantation,  2007, 84(9), 1191-1199.
[http://dx.doi.org/10.1097/01.tp.0000287541.53389.be] [PMID:  17998876] 
[39] 
Guan, X.; Rodriguez-Cruz, V.; Morris, M.E. Cellular uptake of MCT1 inhibitors AR-C155858 and AZD3965 and their effects on MCT-mediated transport of L-lactate in murine 4T1 breast tumor cancer cells. AAPS J.,  2019, 21(2), 13.
[http://dx.doi.org/10.1208/s12248-018-0279-5] [PMID:  30617815] 
[40] 
Beloueche-Babari, M.; Wantuch, S.; Casals Galobart, T.; Koniordou, M.; Parkes, H.G.; Arunan, V.; Chung, Y.L.; Eykyn, T.R.; Smith, P.D.; Leach, M.O. MCT1 inhibitor AZD3965 increases mitochondrial metabolism, facilitating combination therapy and noninvasive magnetic resonance spectroscopy. Cancer Res.,  2017, 77(21), 5913-5924.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2686] [PMID:  28923861] 
[41] 
Gurrapu, S.; Jonnalagadda, S.K.; Alam, M.A.; Ronayne, C.T.; Nelson, G.L.; Solano, L.N.; Lueth, E.A.; Drewes, L.R.; Mereddy, V.R. Coumarin carboxylic acids as monocarboxylate transporter 1 inhibitors: In vitro and in vivo studies as potential anticancer agents. Bioorg. Med. Chem. Lett.,  2016, 26(14), 3282-3286.
[http://dx.doi.org/10.1016/j.bmcl.2016.05.054] [PMID:  27241692] 
[42] 
Pierre, K.; Pellerin, L.; Debernardi, R.; Riederer, B.M.; Magistretti, P.J. Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy. Neuroscience,  2000, 100(3), 617-627.
[http://dx.doi.org/10.1016/S0306-4522(00)00294-3] [PMID:  11098125] 
[43] 
Tadi, M.; Allaman, I.; Lengacher, S.; Grenningloh, G.; Magistretti, P.J. Learning-induced gene expression in the hippocampus reveals a role of neuron - astrocyte metabolic coupling in long term memory. PLoS One,  2015, 10(10)e0141568
[http://dx.doi.org/10.1371/journal.pone.0141568] [PMID:  26513352] 
[44] 
Ljubisavljevic, S.; Stojanovic, I.; Pavlovic, R.; Sokolovic, D.; Pavlovic, D.; Cvetkovic, T.; Stevanovic, I. Modulation of nitric oxide synthase by arginase and methylated arginines during the acute phase of experimental multiple sclerosis. J. Neurol. Sci.,  2012, 318(1-2), 106-111.
[http://dx.doi.org/10.1016/j.jns.2012.03.015] [PMID:  22507752] 
[45] 
Hill, K.E.; Zollinger, L.V.; Watt, H.E.; Carlson, N.G.; Rose, J.W. Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: Distribution, cellular expression and association with myelin damage. J. Neuroimmunol.,  2004, 151(1-2), 171-179.
[http://dx.doi.org/10.1016/j.jneuroim.2004.02.005] [PMID:  15145615] 
[46] 
Tang, X.; Lan, M.; Zhang, M.; Yao, Z. Effect of nitric oxide to axonal degeneration in multiple sclerosis via downregulating monocarboxylate transporter 1 in oligodendrocytes. Nitric Oxide,  2017, 67, 75-80.
[http://dx.doi.org/10.1016/j.niox.2017.04.004] [PMID:  28392448] 
[47] 
Tekkök, S.B.; Brown, A.M.; Westenbroek, R.; Pellerin, L.; Ransom, B.R. Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity. J. Neurosci. Res.,  2005, 81(5), 644-652.
[http://dx.doi.org/10.1002/jnr.20573] [PMID:  16015619] 
[48] 
Lee, Y.; Morrison, B.M.; Li, Y.; Lengacher, S.; Farah, M.H.; Hoffman, P.N.; Liu, Y.; Tsingalia, A.; Jin, L.; Zhang, P.W.; Pellerin, L.; Magistretti, P.J.; Rothstein, J.D. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature,  2012, 487(7408), 443-448.
[http://dx.doi.org/10.1038/nature11314] [PMID:  22801498] 
[49] 
Domènech-Estévez, E.; Baloui, H.; Repond, C.; Rosafio, K.; Médard, J.J.; Tricaud, N.; Pellerin, L.; Chrast, R. Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination. J. Neurosci.,  2015, 35(10), 4151-4156.
[http://dx.doi.org/10.1523/JNEUROSCI.3534-14.2015] [PMID:  25762662] 
[50] 
Morrison, B.M.; Tsingalia, A.; Vidensky, S.; Lee, Y.; Jin, L.; Farah, M.H.; Lengacher, S.; Magistretti, P.J.; Pellerin, L.; Rothstein, J.D. Deficiency in Monocarboxylate Transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush. Exp. Neurol.,  2015, 263, 325-338.
[http://dx.doi.org/10.1016/j.expneurol.2014.10.018] [PMID:  25447940] 
[51] 
Moreira, T.J.; Pierre, K.; Maekawa, F.; Repond, C.; Cebere, A.; Liljequist, S.; Pellerin, L. Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells. J. Cereb. Blood Flow Metab.,  2009, 29(7), 1273-1283.
[http://dx.doi.org/10.1038/jcbfm.2009.50] [PMID:  19401710] 
[52] 
Rosafio, K.; Castillo, X.; Hirt, L.; Pellerin, L. Cell-specific modulation of monocarboxylate transporter expression contributes to the metabolic reprograming taking place following cerebral ischemia. Neuroscience,  2016, 317, 108-120.
[http://dx.doi.org/10.1016/j.neuroscience.2015.12.052] [PMID:  26751713] 
[53] 
Geng, X.; Fu, P.; Ji, X.; Peng, C.; Fredrickson, V.; Sy, C.; Meng, R.; Ling, F.; Du, H.; Tan, X.; Hüttemann, M.; Guthikonda, M.; Ding, Y. Synergetic neuroprotection of normobaric oxygenation and ethanol in ischemic stroke through improved oxidative mechanism. Stroke,  2013, 44(5), 1418-1425.
[http://dx.doi.org/10.1161/STROKEAHA.111.000315] [PMID:  23512978] 
[54] 
Geng, X.; Elmadhoun, O.; Peng, C.; Ji, X.; Hafeez, A.; Liu, Z.; Du, H.; Rafols, J.A.; Ding, Y. Ethanol and normobaric oxygen: Novel approach in modulating pyruvate dehydrogenase complex after severe transient and permanent ischemic stroke. Stroke,  2015, 46(2), 492-499.
[http://dx.doi.org/10.1161/STROKEAHA.114.006994] [PMID:  25563647] 
[55] 
Geng, X.; Sy, C.A.; Kwiecien, T.D.; Ji, X.; Peng, C.; Rastogi, R.; Cai, L.; Du, H.; Brogan, D.; Singh, S.; Rafols, J.A.; Ding, Y. Reduced cerebral monocarboxylate transporters and lactate levels by ethanol and normobaric oxygen therapy in severe transient and permanent ischemic stroke. Brain Res.,  2015, 1603, 65-75.
[http://dx.doi.org/10.1016/j.brainres.2015.01.040] [PMID:  25641040] 
[56] 
Gray, A.L.; Coleman, D.T.; Shi, R.; Cardelli, J.A. Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity. Oncotarget,  2016, 7(22), 32695-32706.
[http://dx.doi.org/10.18632/oncotarget.9016] [PMID:  27127175] 
[57] 
Gatenby, R.A.; Gillies, R.J. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer,  2004, 4(11), 891-899.
[http://dx.doi.org/10.1038/nrc1478] [PMID:  15516961] 
[58] 
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell,  2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID:  21376230] 
[59] 
Granja, S.; Pinheiro, C.; Reis, R.M.; Martinho, O.; Baltazar, F. Glucose addiction in cancer therapy: Advances and drawbacks. Curr. Drug Metab.,  2015, 16(3), 221-242.
[http://dx.doi.org/10.2174/1389200216666150602145145] [PMID:  26504932] 
[60] 
Chiche, J.; Brahimi-Horn, M.C.; Pouysségur, J. Tumour hypoxia induces a metabolic shift causing acidosis: A common feature in cancer. J. Cell. Mol. Med.,  2010, 14(4), 771-794.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00994.x] [PMID:  20015196] 
[61] 
Pinheiro, C.; Reis, R.M.; Ricardo, S.; Longatto-Filho, A.; Schmitt, F.; Baltazar, F. Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44. J. Biomed. Biotechnol.,  2010, 2010427694
[http://dx.doi.org/10.1155/2010/427694] [PMID:  20454640] 
[62] 
Márquez, J.; Alonso, F.J.; Matés, J.M.; Segura, J.A.; Martín-Rufián, M.; Campos-Sandoval, J.A. Glutamine addiction in gliomas. Neurochem. Res.,  2017, 42(6), 1735-1746.
[http://dx.doi.org/10.1007/s11064-017-2212-1] [PMID:  28281102] 
[63] 
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.; Porporato, P.E.; Sonveaux, P. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle,  2016, 15(1), 72-83.
[http://dx.doi.org/10.1080/15384101.2015.1120930] [PMID:  26636483] 
[64] 
Hertz, L.; Chen, Y. Integration between glycolysis and glutamate-glutamine cycle flux may explain preferential glycolytic increase during brain activation, requiring glutamate. Front. Integr. Nuerosci.,  2017, 11, 18.
[http://dx.doi.org/10.3389/fnint.2017.00018] [PMID:  28890689] 
[65] 
Wang, L.; Li, J.J.; Guo, L.Y.; Li, P.; Zhao, Z.; Zhou, H.; Di, L.J. Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4. Oncogenesis,  2018, 7(3), 26.
[http://dx.doi.org/10.1038/s41389-018-0036-8] [PMID:  29540733] 
[66] 
Chen, J.; Herrup, K. Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid and H2O2-induced stress. PLoS One,  2012, 7(3)e33177
[http://dx.doi.org/10.1371/journal.pone.0033177] [PMID:  22413000] 
[67] 
Cardaci, S.; Rizza, S.; Filomeni, G.; Bernardini, R.; Bertocchi, F.; Mattei, M.; Paci, M.; Rotilio, G.; Ciriolo, M.R. Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1. Cancer Res.,  2012, 72(17), 4526-4536.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-1741] [PMID:  22773663] 
[68] 
Chaudhry, F.A.; Schmitz, D.; Reimer, R.J.; Larsson, P.; Gray, A.T.; Nicoll, R.; Kavanaugh, M.; Edwards, R.H. Glutamine uptake by neurons: Interaction of protons with system a transporters. J. Neurosci.,  2002, 22(1), 62-72.
[http://dx.doi.org/10.1523/JNEUROSCI.22-01-00062.2002] [PMID:  11756489] 
[69] 
Ren, N.S.X.; Ji, M.; Tokar, E.J.; Busch, E.L.; Xu, X.; Lewis, D.; Li, X.; Jin, A.; Zhang, Y.; Wu, W.K.K.; Huang, W.; Li, L.; Fargo, D.C.; Keku, T.O.; Sandler, R.S.; Li, X. Haploinsufficiency of SIRT1 enhances glutamine metabolism and promotes cancer development. Curr. Biol.,  2017, 27(4), 483-494.
[http://dx.doi.org/10.1016/j.cub.2016.12.047] [PMID:  28162896] 
[70] 
Yao, Z.Q.; Zhang, X.; Zhen, Y.; He, X.Y.; Zhao, S.; Li, X.F.; Yang, B.; Gao, F.; Guo, F.Y.; Fu, L.; Liu, X.Z.; Duan, C.Z. A novel small-molecule activator of sirtuin-1 induces autophagic cell death/mitophagy as a potential therapeutic strategy in glioblastoma. Cell Death Dis.,  2018, 9(7), 767.
[http://dx.doi.org/10.1038/s41419-018-0799-z] [PMID:  29991742] 
[71] 
Li, Y.; Chen, X.; Cui, Y.; Wei, Q.; Chen, S.; Wang, X. Effects of SIRT1 silencing on viability, invasion and metastasis of human glioma cell lines. Oncol. Lett.,  2019, 17(4), 3701-3708.
[http://dx.doi.org/10.3892/ol.2019.10063] [PMID:  30930981] 
[72] 
Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin.,  2012, 62(1), 10-29.
[http://dx.doi.org/10.3322/caac.20138] [PMID:  22237781] 
[73] 
Morais-Santos, F.; Granja, S.; Miranda-Gonçalves, V.; Moreira, A.H.J.; Queirós, S.; Vilaça, J.L.; Schmitt, F.C.; Longatto-Filho, A.; Paredes, J.; Baltazar, F.; Pinheiro, C. Targeting lactate transport suppresses in vivo breast tumour growth. Oncotarget,  2015, 6(22), 19177-19189.
[http://dx.doi.org/10.18632/oncotarget.3910] [PMID:  26203664] 
[74] 
Miranda-Gonçalves, V.; Honavar, M.; Pinheiro, C.; Martinho, O.; Pires, M.M.; Pinheiro, C.; Cordeiro, M.; Bebiano, G.; Costa, P.; Palmeirim, I.; Reis, R.M.; Baltazar, F. Monocarboxylate Transporters (MCTs) in gliomas: Expression and exploitation as therapeutic targets. Neuro-oncol.,  2013, 15(2), 172-188.
[http://dx.doi.org/10.1093/neuonc/nos298] [PMID:  23258846] 
[75] 
Morais-Santos, F.; Miranda-Gonçalves, V.; Pinheiro, S.; Vieira, A.F.; Paredes, J.; Schmitt, F.C.; Baltazar, F.; Pinheiro, C. Differential sensitivities to lactate transport inhibitors of breast cancer cell lines. Endocr. Relat. Cancer,  2013, 21(1), 27-38.
[http://dx.doi.org/10.1530/ERC-13-0132] [PMID:  24174370] 
[76] 
Miranda-Gonçalves, V.; Granja, S.; Martinho, O.; Honavar, M.; Pojo, M.; Costa, B.M.; Pires, M.M.; Pinheiro, C.; Cordeiro, M.; Bebiano, G.; Costa, P.; Reis, R.M.; Baltazar, F.; Cordeiro, M. Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas. Oncotarget,  2016, 7(29), 46335-46353.
[http://dx.doi.org/10.18632/oncotarget.10114] [PMID:  27331625] 
[77] 
Romero-Garcia, S.; Moreno-Altamirano, M.M.; Prado-Garcia, H.; Sánchez-García, F.J. Lactate contribution to the tumor microenvironment: Mechanisms, effects on immune cells and therapeutic relevance. Front. Immunol.,  2016, 7, 52.
[http://dx.doi.org/10.3389/fimmu.2016.00052] [PMID:  26909082] 
[78] 
Romero-Cordoba, S.L.; Rodriguez-Cuevas, S.; Bautista-Pina, V.; Maffuz-Aziz, A.; D’Ippolito, E.; Cosentino, G.; Baroni, S.; Iorio, M.V.; Hidalgo-Miranda, A. Loss of function of miR-342-3p results in MCT1 over-expression and contributes to oncogenic metabolic reprogramming in triple negative breast cancer. Sci. Rep.,  2018, 8(1), 12252.
[http://dx.doi.org/10.1038/s41598-018-29708-9] [PMID:  30115973] 
[79] 
Johnson, J.M.; Cotzia, P.; Fratamico, R.; Mikkilineni, L.; Chen, J.; Colombo, D.; Mollaee, M.; Whitaker-Menezes, D.; Domingo-Vidal, M.; Lin, Z.; Zhan, T.; Tuluc, M.; Palazzo, J.; Birbe, R.C.; Martinez-Outschoorn, U.E. MCT1 in invasive ductal carcinoma: Monocarboxylate metabolism and aggressive breast cancer. Front. Cell Dev. Biol.,  2017, 5, 27.
[http://dx.doi.org/10.3389/fcell.2017.00027] [PMID:  28421181] 
[80] 
Li, Z.; Wu, Q.; Sun, S.; Wu, J.; Li, J.; Zhang, Y.; Wang, C.; Yuan, J.; Sun, S. Monocarboxylate transporters in breast cancer and adipose tissue are novel biomarkers and potential therapeutic targets. Biochem. Biophys. Res. Commun.,  2018, 501(4), 962-967.
[http://dx.doi.org/10.1016/j.bbrc.2018.05.091] [PMID:  29775610] 
[81] 
Shi, H.; Jiang, H.; Wang, L.; Cao, Y.; Liu, P.; Xu, X.; Wang, Y.; Sun, L.; Niu, H. Overexpression of monocarboxylate anion transporter 1 and 4 in T24-induced cancer-associated fibroblasts regulates the progression of bladder cancer cells in a 3D microfluidic device. Cell Cycle,  2015, 14(19), 3058-3065.
[http://dx.doi.org/10.1080/15384101.2015.1053666] [PMID:  26125467] 
[82] 
Sonveaux, P.; Végran, F.; Schroeder, T.; Wergin, M.C.; Verrax, J.; Rabbani, Z.N.; De Saedeleer, C.J.; Kennedy, K.M.; Diepart, C.; Jordan, B.F.; Kelley, M.J.; Gallez, B.; Wahl, M.L.; Feron, O.; Dewhirst, M.W. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Invest.,  2008, 118(12), 3930-3942.
[http://dx.doi.org/10.1172/JCI36843] [PMID:  19033663] 
[83] 
Feron, O. Pyruvate into lactate and back: From the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother. Oncol.,  2009, 92(3), 329-333.
[http://dx.doi.org/10.1016/j.radonc.2009.06.025] [PMID:  19604589] 
[84] 
Syed, I.S.; Pedram, A.; Farhat, W.A. Role of sonic hedgehog (Shh) signaling in bladder cancer stemness and tumorigenesis. Curr. Urol. Rep.,  2016, 17(2), 11.
[http://dx.doi.org/10.1007/s11934-015-0568-9] [PMID:  26757905] 
[85] 
Zhang, G.; Zhang, Y.; Dong, D.; Wang, F.; Ma, X.; Guan, F.; Sun, L. MCT1 regulates aggressive and metabolic phenotypes in bladder cancer. J. Cancer,  2018, 9(14), 2492-2501.
[http://dx.doi.org/10.7150/jca.25257] [PMID:  30026847] 
[86] 
Afonso, J.; Santos, L.L.; Miranda-Gonçalves, V.; Morais, A.; Amaro, T.; Longatto-Filho, A.; Baltazar, F. CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance. Mol. Carcinog.,  2015, 54(11), 1451-1466.
[http://dx.doi.org/10.1002/mc.22222] [PMID:  25263481] 
[87] 
Riemenschneider, M.J.; Reifenberger, G. Molecular neuropathology of gliomas. Int. J. Mol. Sci.,  2009, 10(1), 184-212.
[http://dx.doi.org/10.3390/ijms10010184] [PMID:  19333441] 
[88] 
Stupp, R.; Hegi, M.E.; Mason, W.P.; van den Bent, M.J.; Taphoorn, M.J.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A.A.; Gijtenbeek, J.; Marosi, C.; Vecht, C.J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J.G.; Mirimanoff, R.O. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol.,  2009, 10(5), 459-466.
[http://dx.doi.org/10.1016/S1470-2045(09)70025-7] [PMID:  19269895] 
[89] 
Oudard, S.; Arvelo, F.; Miccoli, L.; Apiou, F.; Dutrillaux, A.M.; Poisson, M.; Dutrillaux, B.; Poupon, M.F.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A.A.; Gijtenbeek, J.; Marosi, C.; Vecht, C.J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J.G.; Mirimanoff, R.O. High glycolysis in gliomas despite low hexokinase transcription and activity correlated to chromosome 10 loss. Br. J. Cancer,  1996, 74(6), 839-845.
[http://dx.doi.org/10.1038/bjc.1996.446] [PMID:  8826847] 
[90] 
Tabatabaei, P.; Bergström, P.; Henriksson, R.; Bergenheim, A.T. Glucose metabolites, glutamate and glycerol in malignant glioma tumours during radiotherapy. J. Neurooncol.,  2008, 90(1), 35-39.
[http://dx.doi.org/10.1007/s11060-008-9625-2] [PMID:  18563297] 
[91] 
Miranda-Gonçalves, V.; Honavar, M.; Pinheiro, C.; Martinho, O.; Pires, M.M.; Pinheiro, C.; Cordeiro, M.; Bebiano, G.; Costa, P.; Palmeirim, I.; Reis, R.M.; Baltazar, F. Monocarboxylate transporters (MCTs) in gliomas: Expression and exploitation as therapeutic targets. Neuro-oncol.,  2013, 15(2), 172-188.
[http://dx.doi.org/10.1093/neuonc/nos298] [PMID:  23258846] 
[92] 
Duan, K.; Liu, Z.J.; Hu, S.Q.; Huo, H.Y.; Xu, Z.R.; Ruan, J.F.; Sun, Y.; Dai, L.P.; Yan, C.B.; Xiong, W.; Cui, Q.H.; Yu, H.J.; Yu, M.; Qin, Y. Lactic acid induces lactate transport and glycolysis/OXPHOS interconversion in glioblastoma. Biochem. Biophys. Res. Commun.,  2018, 503(2), 888-894.
[http://dx.doi.org/10.1016/j.bbrc.2018.06.092] [PMID:  29928884] 
[93] 
Miranda-Gonçalves, V.; Bezerra, F.; Costa-Almeida, R.; Freitas-Cunha, M.; Soares, R.; Martinho, O.; Reis, R.M.; Pinheiro, C.; Baltazar, F. Monocarboxylate transporter 1 is a key player in glioma-endothelial cell crosstalk. Mol. Carcinog.,  2017, 56(12), 2630-2642.
[http://dx.doi.org/10.1002/mc.22707] [PMID:  28762551] 
[94] 
Park, S.J.; Smith, C.P.; Wilbur, R.R.; Cain, C.P.; Kallu, S.R.; Valasapalli, S.; Sahoo, A.; Guda, M.R.; Tsung, A.J.; Velpula, K.K. An overview of MCT1 and MCT4 in GBM: Small molecule transporters with large implications. Am. J. Cancer Res.,  2018, 8(10), 1967-1976.
[PMID:  30416849] 
[95] 
Zhang, P.; Ma, J.; Gao, J.; Liu, F.; Sun, X.; Fang, F.; Zhao, S.; Liu, H. Downregulation of monocarboxylate transporter 1 inhibits the invasion and migration through suppression of the PI3K/Akt signaling pathway in human nasopharyngeal carcinoma cells. J. Bioenerg. Biomembr.,  2018, 50(4), 271-281.
[http://dx.doi.org/10.1007/s10863-018-9763-y] [PMID:  29882205] 
[96] 
Silva, L.S.; Goncalves, L.G.; Silva, F.; Domingues, G.; Maximo, V.; Ferreira, J.; Lam, E.W.F.; Dias, S.; Felix, A.; Serpa, J. STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment. Tumour Biol.,  2016, 37(4), 5385-5395.
[http://dx.doi.org/10.1007/s13277-015-4385-z] [PMID:  26563366] 
[97] 
Mehibel, M.; Ortiz-Martinez, F.; Voelxen, N.; Boyers, A.; Chadwick, A.; Telfer, B.A.; Mueller-Klieser, W.; West, C.M.; Critchlow, S.E.; Williams, K.J.; Stratford, I.J. Statin-induced metabolic reprogramming in head and neck cancer: A biomarker for targeting monocarboxylate transporters. Sci. Rep.,  2018, 8(1), 16804.
[http://dx.doi.org/10.1038/s41598-018-35103-1] [PMID:  30429503] 
[98] 
Battista, M.J.; Goetze, K.; Schmidt, M.; Cotarelo, C.; Weyer-Elberich, V.; Hasenburg, A.; Mueller-Klieser, W.; Walenta, S. Feasibility of induced metabolic bioluminescence imaging in advanced ovarian cancer patients: First results of a pilot study. J. Cancer Res. Clin. Oncol.,  2016, 142(9), 1909-1916.
[http://dx.doi.org/10.1007/s00432-016-2200-x] [PMID:  27342420] 
[99] 
Kim, Y.; Choi, J.W.; Lee, J.H.; Kim, Y.S. Expression of lactate/H+ symporters MCT1 and MCT4 and their chaperone CD147 predicts tumor progression in clear cell renal cell carcinoma: Immunohistochemical and the Cancer Genome Atlas data analyses. Hum. Pathol.,  2015, 46(1), 104-112.
[http://dx.doi.org/10.1016/j.humpath.2014.09.013] [PMID:  25456395] 
[100] 
Ambrosetti, D.; Dufies, M.; Dadone, B.; Durand, M.; Borchiellini, D.; Amiel, J.; Pouyssegur, J.; Rioux-Leclercq, N.; Pages, G.; Burel-Vandenbos, F.; Mazure, N.M. The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma. PLoS One,  2018, 13(2)e0193477
[http://dx.doi.org/10.1371/journal.pone.0193477] [PMID:  29481555] 
[101] 
Fisel, P.; Schaeffeler, E.; Schwab, M. Clinical and functional relevance of the monocarboxylate transporter family in disease pathophysiology and drug therapy. Clin. Transl. Sci.,  2018, 11(4), 352-364.
[http://dx.doi.org/10.1111/cts.12551] [PMID:  29660777] 
[102] 
Kido, Y.; Tamai, I.; Okamoto, M.; Suzuki, F.; Tsuji, A. Functional clarification of MCT1-mediated transport of monocarboxylic acids at the blood-brain barrier using in vitro cultured cells and in vivo BUI studies. Pharm. Res.,  2000, 17(1), 55-62.
[http://dx.doi.org/10.1023/A:1007518525161] [PMID:  10714609] 
[103] 
Hartley, M.D.; Altowaijri, G.; Bourdette, D. Remyelination and multiple sclerosis: Therapeutic approaches and challenges. Curr. Neurol. Neurosci. Rep.,  2014, 14(10), 485.
[http://dx.doi.org/10.1007/s11910-014-0485-1] [PMID:  25108747] 
[104] 
Harlow, D.E.; Honce, J.M.; Miravalle, A.A. Remyelination therapy in multiple sclerosis. Front. Neurol.,  2015, 6, 257.
[http://dx.doi.org/10.3389/fneur.2015.00257] [PMID:  26696956] 
[105] 
Dugas, J.C.; Cuellar, T.L.; Scholze, A.; Ason, B.; Ibrahim, A.; Emery, B.; Zamanian, J.L.; Foo, L.C.; McManus, M.T.; Barres, B.A. Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron,  2010, 65(5), 597-611.
[http://dx.doi.org/10.1016/j.neuron.2010.01.027] [PMID:  20223197] 
[106] 
Liu, S.; Ren, C.; Qu, X.; Wu, X.; Dong, F.; Chand, Y.K.; Fan, H.; Yao, R.; Geng, D. miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1. Eur. J. Neurosci.,  2017, 45(2), 249-259.
[http://dx.doi.org/10.1111/ejn.13485] [PMID:  27873367] 
[107] 
Rice, A.S.; Maton, S. Postherpetic Neuralgia Study Group. Gabapentin in postherpetic neuralgia: A randomised, double blind, placebo controlled study. Pain,  2001, 94(2), 215-224.
[http://dx.doi.org/10.1016/S0304-3959(01)00407-9] [PMID:  11690735] 
[108] 
Cundy, K.C.; Branch, R.; Chernov-Rogan, T.; Dias, T.; Estrada, T.; Hold, K.; Koller, K.; Liu, X.; Mann, A.; Panuwat, M.; Raillard, S.P.; Upadhyay, S.; Wu, Q.Q.; Xiang, J.N.; Yan, H.; Zerangue, N.; Zhou, C.X.; Barrett, R.W.; Gallop, M.A. XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters. J. Pharmacol. Exp. Ther.,  2004, 311(1), 315-323.
[http://dx.doi.org/10.1124/jpet.104.067934] [PMID:  15146028] 
[109] 
Cundy, K.C.; Sastry, S.; Luo, W.; Zou, J.; Moors, T.L.; Canafax, D.M. Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J. Clin. Pharmacol.,  2008, 48(12), 1378-1388.
[http://dx.doi.org/10.1177/0091270008322909] [PMID:  18827074] 
[110] 
Boquet, G.; Barakat, L.; Paly, J.; Djiane, J.; Dufy, B. Involvement of both calcium influx and calcium mobilization in growth hormone-induced [Ca2+]i increases in Chinese hamster ovary cells. Mol. Cell. Endocrinol.,  1997, 131(1), 109-120.
[http://dx.doi.org/10.1016/S0303-7207(97)00105-6] [PMID:  9256369] 
[111] 
Venishetty, V.K.; Samala, R.; Komuravelli, R.; Kuncha, M.; Sistla, R.; Diwan, P.V. β-Hydroxybutyric acid grafted solid lipid nanoparticles: A novel strategy to improve drug delivery to brain. Nanomedicine (Lond.),  2013, 9(3), 388-397.
[http://dx.doi.org/10.1016/j.nano.2012.08.004] [PMID:  22960191] 
[112] 
zur Mühlen, A.; Schwarz, C.; Mehnert, W. Solid Lipid Nanoparticles (SLN) for controlled drug delivery-drug release and release mechanism. Eur. J. Pharm. Biopharm.,  1998, 45(2), 149-155.
[http://dx.doi.org/10.1016/S0939-6411(97)00150-1] [PMID:  9704911] 
[113] 
Doherty, J.R.; Cleveland, J.L. Targeting lactate metabolism for cancer therapeutics. J. Clin. Invest.,  2013, 123(9), 3685-3692.
[http://dx.doi.org/10.1172/JCI69741] [PMID:  23999443] 
[114] 
Pinheiro, C.; Albergaria, A.; Paredes, J.; Sousa, B.; Dufloth, R.; Vieira, D.; Schmitt, F.; Baltazar, F. Monocarboxylate transporter 1 is up-regulated in basal-like breast carcinoma. Histopathology,  2010, 56(7), 860-867.
[http://dx.doi.org/10.1111/j.1365-2559.2010.03560.x] [PMID:  20636790] 
[115] 
Chen, H.; Wang, L.; Beretov, J.; Hao, J.; Xiao, W.; Li, Y. Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression. Clin. Exp. Metastasis,  2010, 27(8), 557-569.
[http://dx.doi.org/10.1007/s10585-010-9345-9] [PMID:  20658178] 
[116] 
Birsoy, K.; Wang, T.; Possemato, R.; Yilmaz, O.H.; Koch, C.E.; Chen, W.W.; Hutchins, A.W.; Gultekin, Y.; Peterson, T.R.; Carette, J.E.; Brummelkamp, T.R.; Clish, C.B.; Sabatini, D.M. MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors. Nat. Genet.,  2013, 45(1), 104-108.
[http://dx.doi.org/10.1038/ng.2471] [PMID:  23202129] 
[117] 
Prasad, C.P.; Södergren, K.; Andersson, T. Reduced production and uptake of lactate are essential for the ability of WNT5A signaling to inhibit breast cancer cell migration and invasion. Oncotarget,  2017, 8(42), 71471-71488.
[http://dx.doi.org/10.18632/oncotarget.17277] [PMID:  29069720] 
[118] 
Morais-Santos, F.; Miranda-Gonçalves, V.; Pinheiro, S.; Vieira, A.F.; Paredes, J.; Schmitt, F.C.; Baltazar, F.; Pinheiro, C. Differential sensitivities to lactate transport inhibitors of breast cancer cell lines. Endocr. Relat. Cancer,  2013, 21(1), 27-38.
[http://dx.doi.org/10.1530/ERC-13-0132] [PMID:  24174370] 
[119] 
Morais-Santos, F.; Granja, S.; Miranda-Gonçalves, V.; Moreira, A.H.J.; Queirós, S.; Vilaça, J.L.; Schmitt, F.C.; Longatto-Filho, A.; Paredes, J.; Baltazar, F.; Pinheiro, C. Targeting lactate transport suppresses in vivo breast tumour growth. Oncotarget,  2015, 6(22), 19177-19189.
[http://dx.doi.org/10.18632/oncotarget.3910] [PMID:  26203664] 
Cite As
Current Drug Metabolism

Monocarboxylate Transporter 1 in Brain Diseases and Cancers

Abstract

Graphical Abstract
