Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Targeting Signalling Cross-Talk between Cancer Cells and Cancer-Associated Fibroblast through Monocarboxylate Transporters in Head and Neck Cancer

Author(s): Vaishali Chandel and Dhruv Kumar*

Volume 21, Issue 11, 2021

Published on: 21 July, 2020

Page: [1369 - 1378] Pages: 10

DOI: 10.2174/1871520620666200721135230

Price: $65

Abstract

Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy affecting more than 600,000 cases worldwide annually, associated with poor prognosis and significant morbidity. HNSCC tumors are dysplastic, with up to 80% fibroblasts. It has been reported that Cancer-Associated Fibroblasts (CAFs) facilitate HNSCC progression. Unlike normal cells, malignant cells often display increased glycolysis, even in the presence of oxygen; a phenomenon known as the Warburg effect. As a consequence, there is an increase in Lactic Acid (LA) production. Earlier, it has been reported that HNSCC tumors exhibit high LA levels that correlate with reduced survival. It has been reported that the activation of the receptor tyrosine kinase, c- MET, by CAF-secreted Hepatocyte Growth Factor (HGF) is a major contributing event in the progression of HNSCC. In nasopharyngeal carcinoma, c-MET inhibition downregulates the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) and NADPH production resulting in apoptosis. Previously, it was demonstrated that HNSCC tumor cells are highly glycolytic. Further, CAFs show a higher capacity to utilize LA as a carbon source to fuel mitochondrial respiration than HNSCC. Earlier, we have reported that in admixed cultures, both cell types increase the expression of Monocarboxylate Transporters (MCTs) for a bidirectional LA transporter. Consequently, MCTs play an important role in signalling cross-talk between cancer cells and cancer associate fibroblast in head and neck cancer, and targeting MCTs would lead to the development of a potential therapeutic approach for head and neck cancer. In this review, we focus on the regulation of MCTs in head and neck cancer through signalling cross-talk between cancer cells and cancer-associated fibroblasts, and targeting this signalling cross talk would lead to the development of a potential therapeutic approach for head and neck cancer.

Keywords: Head and neck cancer, Cancer-Associated Fibroblasts (CAFs), Monocarboxylate Transporters (MCTs), lactic acid, metabolism, c-MET (Mesenchymal Epithelial Transition) factor, Hepatocyte Growth Factor (HGF).

« Previous Next »
Graphical Abstract

[1]
Vigneswaran, N.; Williams, M.D. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac. Surg. Clin. North Am., 2014, 26(2), 123-141.
[http://dx.doi.org/10.1016/j.coms.2014.01.001] [PMID: 24794262]
[2]
Dhull, A.K.; Atri, R.; Dhankhar, R.; Chauhan, A.K.; Kaushal, V. Major risk factors in head and neck cancer: A retrospective analysis of 12-year experiences. World J. Oncol., 2018, 9(3), 80-84.
[http://dx.doi.org/10.14740/wjon1104w] [PMID: 29988794]
[3]
Cognetti, D.M.; Weber, R.S.; Lai, S.Y. Head and neck cancer: An evolving treatment paradigm. Cancer, 2008, 113(7)(Suppl.), 1911-1932.
[http://dx.doi.org/10.1002/cncr.23654] [PMID: 18798532]
[4]
Sounni, N.E.; Noel, A. Targeting the tumor microenvironment for cancer therapy. Clin. Chem., 2013, 59(1), 85-93.
[http://dx.doi.org/10.1373/clinchem.2012.185363] [PMID: 23193058]
[5]
Wang, M.; Zhao, J.; Zhang, L.; Wei, F.; Lian, Y.; Wu, Y.; Gong, Z.; Zhang, S.; Zhou, J.; Cao, K.; Li, X.; Xiong, W.; Li, G.; Zeng, Z.; Guo, C. Role of tumor microenvironment in tumorigenesis. J. Cancer, 2017, 8(5), 761-773.
[http://dx.doi.org/10.7150/jca.17648] [PMID: 28382138]
[6]
Peltanova, B.M. Raudenska.; Masarik, M. Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: A systematic review. Mol. Cancer, 2019, 18, 1-24.
[http://dx.doi.org/10.1186/s12943-019-0983-5]
[7]
Liberti, M.V.; Locasale, J.W. The Warburg Effect: How does it benefit cancer cells? Trends Biochem. Sci., 2016, 41(3), 211-218.
[http://dx.doi.org/10.1016/j.tibs.2015.12.001] [PMID: 26778478]
[8]
Hsieh, Y.T.; Chen, Y.F.; Lin, S.C.; Chang, K.W.; Li, W.C. Targeting cellular metabolism modulates head and neck oncogenesis. Int. J. Mol. Sci., 2019, 20(16), E3960.
[http://dx.doi.org/10.3390/ijms20163960] [PMID: 31416244]
[9]
Kumar, D. Regulation of glycolysis in head and neck squamous cell carcinoma. Postdoc J., 2017, 5(1), 14-28.
[http://dx.doi.org/10.14304/SURYA.JPR.V5N1.4] [PMID: 28191478]
[10]
Sugden, M.C.; Holness, M.J. The pyruvate carboxylase-pyruvate dehydrogenase axis in islet pyruvate metabolism: Going round in circles? Islets, 2011, 3(6), 302-319.
[http://dx.doi.org/10.4161/isl.3.6.17806] [PMID: 21934355]
[11]
San-Millán, I.; Brooks, G.A. Reexamining cancer metabolism: Lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect. Carcinogenesis, 2017, 38, 119-133.
[12]
Pinheiro, C.; Longatto-Filho, A.; Azevedo-Silva, J.; Casal, M.; Schmitt, F.C.; Baltazar, F. Role of monocarboxylate transporters in human cancers: State of the art. J. Bioenerg. Biomembr., 2012, 44(1), 127-139.
[http://dx.doi.org/10.1007/s10863-012-9428-1] [PMID: 22407107]
[13]
Zhu, A.; Daniel Lee, A.; Shim, H. Metabolic PET imaging in cancer detection and therapy response. Semin. Oncol., 2011, 38, 55-69.
[http://dx.doi.org/10.1053/j.seminoncol.2010.11.012] [PMID: 21362516]
[14]
Tao, L.; Huang, G.; Song, H.; Chen, Y.; Chen, L. Cancer associated fibroblasts: An essential role in the tumor microenvironment. Oncol. Lett., 2017, 14(3), 2611-2620.
[http://dx.doi.org/10.3892/ol.2017.6497] [PMID: 28927027]
[15]
Gál, P.; Varinská, L.; Fáber, L.; Novák, Š.; Szabo, P.; Mitrengová, P.; Mirossay, A.; Mučaji, P.; Smetana, K. How signaling molecules regulate tumor microenvironment: Parallels to wound repair. Molecules, 2017, 22(11), 1-17.
[http://dx.doi.org/10.3390/molecules22111818] [PMID: 29072623]
[16]
Öhlund, D.; Elyada, E.; Tuveson, D. Fibroblast heterogeneity in the cancer wound. J. Exp. Med., 2014, 211(8), 1503-1523.
[http://dx.doi.org/10.1084/jem.20140692] [PMID: 25071162]
[17]
Sandberg, T.P.; Stuart, M.P.M.E.; Oosting, J.; Tollenaar, R.A.E.M.; Sier, C.F.M.; Mesker, W.E. Increased expression of cancer-associated fibroblast markers at the invasive front and its association with tumor-stroma ratio in colorectal cancer. BMC Cancer, 2019, 19(1), 284.
[http://dx.doi.org/10.1186/s12885-019-5462-2] [PMID: 30922247]
[18]
Ba, P.; Zhang, X.; Yu, M.; Li, L.; Duan, X.; Wang, M.; Lv, S.; Fu, G.; Yang, P.; Yang, C.; Sun, Q. Cancer associated fibroblasts are distinguishable from peri-tumor fibroblasts by biological characteristics in TSCC. Oncol. Lett., 2019, 18(3), 2484-2490.
[http://dx.doi.org/10.3892/ol.2019.10556] [PMID: 31404347]
[19]
Bredell, M.G.; Ernst, J.; El-Kochairi, I.; Dahlem, Y.; Ikenberg, K.; Schumann, D.M. Current relevance of hypoxia in head and neck cancer. Oncotarget, 2016, 7(31), 50781-50804.
[http://dx.doi.org/10.18632/oncotarget.9549] [PMID: 27434126]
[20]
Jing, X.; Yang, F.; Shao, C.; Wei, K.; Xie, M.; Shen, H.; Shu, Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol. Cancer, 2019, 18(1), 157.
[http://dx.doi.org/10.1186/s12943-019-1089-9] [PMID: 31711497]
[21]
Ziello, J.E.; Jovin, I.S.; Huang, Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J. Biol. Med., 2007, 80(2), 51-60.
[PMID: 18160990]
[22]
Zhang, Y.; Yang, J.M. Altered energy metabolism in cancer: A unique opportunity for therapeutic intervention. Cancer Biol. Ther., 2013, 14(2), 81-89.
[http://dx.doi.org/10.4161/cbt.22958] [PMID: 23192270]
[23]
Li, Y.Y.; Zhu, B. Metabolism of cancer cells and immune cells in the tumor microenvironment. Front. Immunol., 2018, 9.
[24]
de la Cruz-López, K.G.; Castro-Muñoz, L.J.; Reyes-Hernández, D.O.; García-Carrancá, A.; Manzo-Merino, J. Lactate in the regulation of tumor microenvironment and therapeutic approaches. Front. Oncol., 2019, 9, 1143.
[http://dx.doi.org/10.3389/fonc.2019.01143] [PMID: 31737570]
[25]
Kumar, D.; New, J.; Vishwakarma, V.; Joshi, R.; Enders, J.; Lin, F.; Dasari, S.; Gutierrez, W.R.; Leef, G.; Ponnurangam, S.; Chavan, H.; Ganaden, L.; Thornton, M.M.; Dai, H.; Tawfik, O.; Straub, J.; Shnayder, Y.; Kakarala, K.; Tsue, T.T.; Girod, D.A.; Van Houten, B.; Anant, S.; Krishnamurthy, P.; Thomas, S.M. Cancer-associated fibroblasts drive glycolysis in a targetable signalling loop implicated in head and neck squamous cell carcinoma progression. Cancer Res., 2018, 78(14), 3769-3782.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-1076] [PMID: 29769197]
[26]
Arnold, L.; Enders, J.; Thomas, S.M. Activated HGF-c-MET axis in head and neck cancer. Cancers (Basel), 2017, 9(12), 1-22.
[http://dx.doi.org/10.3390/cancers9120169] [PMID: 29231907]
[27]
Natan, S.; Tsarfaty, J.; Horev, R.; Haklai, Y.; Kloog, Y.; Tsarfaty, I. Interplay between HGF/SF-Met-Ras signalling, tumor metabolism and blood flow as a potential target for breast cancer therapy. Oncoscience, 2019, 1, 30-38.
[http://dx.doi.org/10.18632/oncoscience.6] [PMID: 25593982]
[28]
Hartmann, S.; Bhola, N.E.; Grandis, J.R. HGF/Met signalling in head and neck cancer: Impact on the tumor microenvironment. Clin. Cancer Res., 2016, 22(16), 4005-4013.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0951] [PMID: 27370607]
[29]
Koontongkaew, S. The tumor microenvironment contribution to development, growth, invasion and metastasis of head and neck squamous cell carcinomas. J. Cancer, 2013, 4(1), 66-83.
[http://dx.doi.org/10.7150/jca.5112] [PMID: 23386906]
[30]
Jang, I.; Beningo, K.A. Integrins, CAFs and mechanical forces in the progression of cancer. Cancers (Basel), 2019, 11(5), 721.
[http://dx.doi.org/10.3390/cancers11050721] [PMID: 31137693]
[31]
Damaghi, M.; Wojtkowiak, J.W.; Gillies, R.J. pH sensing and regulation in cancer. Front. Physiol., 2013, 4, 370.
[http://dx.doi.org/10.3389/fphys.2013.00370] [PMID: 24381558]
[32]
Jones, R.A.; Morris, M.E. Monocarboxylate transporters: Therapeutic targets and prognostic factors in disease. Clin. Pharmacol. Ther., 2017, 100, 454-463.
[33]
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]
[34]
Vijay, N.; Morris, M.E. Role of monocarboxylate transporters in drug delivery to the brain. Curr. Pharm. Des., 2014, 20(10), 1487-1498.
[http://dx.doi.org/10.2174/13816128113199990462] [PMID: 23789956]
[35]
Simões-Sousa, S.; Granja, S.; Pinheiro, C.; Fernandes, D.; Longatto-Filho, A.; Laus, A.C.; Alves, C.D.; Suárez-Peñaranda, J.M.; Pérez-Sayáns, M.; Lopes Carvalho, A.; Schmitt, F.C.; García-García, A.; Baltazar, F. Prognostic significance of monocarboxylate transporter expression in oral cavity tumors. Cell Cycle, 2016, 15(14), 1865-1873.
[http://dx.doi.org/10.1080/15384101.2016.1188239] [PMID: 27232157]
[36]
Romero-Garcia, S.S.; Moreno-Altamirano, M.M.B.; 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.
[37]
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]
[38]
Morris, M.E.; Felmlee, M.A. Overview of the proton-coupled MCT (SLC16A) family of transporters: Characterization, function and role in the transport of the drug of abuse γ-hydroxybutyric acid. AAPS J., 2008, 10(2), 311-321.
[http://dx.doi.org/10.1208/s12248-008-9035-6] [PMID: 18523892]
[39]
Noor, S.I.; Jamali, S.; Ames, S.; Langer, S.; Deitmer, J.W.; Becker, H.M. A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells. eLife, 2018, 7, 1-31.
[http://dx.doi.org/10.7554/eLife.35176] [PMID: 29809145]
[40]
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. 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]
[41]
Pértega-Gomes, N.; Vizcaíno, J.R.; Miranda-Gonçalves, V.; Pinheiro, C.; Silva, J.; Pereira, H.; Monteiro, P.; Henrique, R.M.; Reis, R.M.; Lopes, C.; Baltazar, F. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer, 2011, 11, 312.
[http://dx.doi.org/10.1186/1471-2407-11-312] [PMID: 21787388]
[42]
Yu, L.; Chen, X.; Sun, X.; Wang, L.; Chen, S. The glycolytic switch in tumors: How many players are involved? J. Cancer, 2017, 8(17), 3430-3440.
[http://dx.doi.org/10.7150/jca.21125] [PMID: 29151926]
[43]
Pinheiro, C.; Garcia, E.A.; Morais-Santos, F.; Moreira, M.A.; Almeida, F.M.; Jubé, L.F.; Queiroz, G.S.; Paula, É.C.; Andreoli, M.A.; Villa, L.L.; Longatto-Filho, A.; Baltazar, F. Reprogramming energy metabolism and inducing angiogenesis: Co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas. BMC Cancer, 2015, 15, 835.
[http://dx.doi.org/10.1186/s12885-015-1842-4] [PMID: 26525902]
[44]
Contreras-Baeza, Y. MCT4 is a high affinity transporter capable of exporting lactate in high-lactate environments. bioRxiv, 2019, 4, 586966.
[45]
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. 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]
[46]
Doherty, J.R.; Cleveland, J.L.; 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]
[47]
Stephanie, S.T.; Amber, N.H.; Kira, T.P.; Miriam, M.M.; Kehui, W. Lactate/pyruvate transporter MCT1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer. Cancer Metab., 2016, 4, 20.
[48]
Ždralević, M.; Marchiq, I.; de Padua, M.M.C.; Parks, S.K.; Pouysségur, J. Metabolic plasiticy in cancers-distinct role of glycolytic enzymes GPI, LDHs or membrane transporters MCTs. Front. Oncol., 2017, 7, 313.
[http://dx.doi.org/10.3389/fonc.2017.00313] [PMID: 29326883]
[49]
Brooks, G.A. Cell-cell and intracellular lactate shuttles. J. Physiol., 2009, 587(Pt 23), 5591-5600.
[http://dx.doi.org/10.1113/jphysiol.2009.178350] [PMID: 19805739]
[50]
Marchiq, I.; Pouysségur, J. Hypoxia, cancer metabolism and the therapeutic benefit of targeting lactate/H(+) symporters. J. Mol. Med. (Berl.), 2016, 94(2), 155-171.
[http://dx.doi.org/10.1007/s00109-015-1307-x] [PMID: 26099350]
[51]
Lu, J.; Tan, M.; Cai, Q. The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett., 2015, 356(2 Pt A), 156-164.
[http://dx.doi.org/10.1016/j.canlet.2014.04.001] [PMID: 24732809]
[52]
Kane, D.A. Lactate oxidation at the mitochondria: A lactate-malate-aspartate shuttle at work. Front. Neurooncol., 2014, 8, 1-6.
[53]
Payen, V.L.; Mina, E.; Van Hée, V.F.; Porporato, P.E.; Sonveaux, P. Monocarboxylate transporters in cancer. Mol. Metab., 2020, 33, 48-66.
[http://dx.doi.org/10.1016/j.molmet.2019.07.006] [PMID: 31395464]
[54]
Muramatsu, T. Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners. J. Biochem., 2019, 159, 481-490.
[55]
Plzák, J.; Bouček, J.; Bandúrová, V.; Kolář, M.; Hradilová, M.; Szabo, P.; Lacina, L.; Chovanec, M.; Smetana, K., Jr. The head and neck squamous cell carcinoma microenvironment as a potential target for cancer therapy. Cancers (Basel), 2019, 11(4), e440.
[http://dx.doi.org/10.3390/cancers11040440] [PMID: 30925774]
[56]
Chen, H.H.W.; Kuo, M.T. Improving radiotherapy in cancer treatment: Promises and challenges. Oncotarget, 2017, 8(37), 62742-62758.
[http://dx.doi.org/10.18632/oncotarget.18409] [PMID: 28977985]
[57]
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]
[58]
Quanz, M.; Bender, E.; Kopitz, C.; Grünewald, S.; Schlicker, A.; Schwede, W.; Eheim, A.; Toschi, L.; Neuhaus, R.; Richter, C.; Toedling, J.; Merz, C.; Lesche, R.; Kamburov, A.; Siebeneicher, H.; Bauser, M.; Hägebarth, A. Preclinical efficacy of the novel monocarboxylate transporter 1 inhibitor BAY-8002 and associated markers of resistance. Mol. Cancer Ther., 2018, 17(11), 2285-2296.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-1253] [PMID: 30115664]
[59]
Payen, V.L.; Mina, E.; Van Hee, V.F.; Porporato, P.E.; Sonveaux, P. Monocarboxylate transporters in cancer. Mol. Metab., 2019, 33, 48-66.
[PMID: 31395464]
[60]
Pisarsky, L.; Bill, R.; Fagiani, E.; Dimeloe, S.; Goosen, R.W.; Hagmann, J.; Hess, C.; Christofori, G. Targeting metabolic symbiosis to overcome resistance to anti-angiogenic therapy. Cell Rep., 2016, 15(6), 1161-1174.
[http://dx.doi.org/10.1016/j.celrep.2016.04.028] [PMID: 27134168]
[61]
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]
[62]
Koukourakis, M.I.; Giatromanolaki, A.; Harris, A.L.; Sivridis, E. Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: A metabolic survival role for tumor-associated stroma. Cancer Res., 2006, 66(2), 632-637.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3260] [PMID: 16423989]
[63]
Avagliano, A.; Granato, G.; Ruocco, M.R.; Romano, V.; Belviso, I.; Carfora, A.; Montagnani, S.; Arcucci, A. Metabolic reprogramming of cancer associated fibroblasts: The slavery of stromal fibroblasts. BioMed Res. Int., 2018, 2018, 6075403.
[http://dx.doi.org/10.1155/2018/6075403] [PMID: 29967776]
[64]
Hao, J.; Chen, H.; Madigan, M.C.; Cozzi, P.J.; Beretov, J.; Xiao, W.; Delprado, W.J.; Russell, P.J.; Li, Y. Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression. Br. J. Cancer, 2010, 103(7), 1008-1018.
[http://dx.doi.org/10.1038/sj.bjc.6605839] [PMID: 20736947]
[65]
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]
[66]
Le Floch, R.; Chiche, J.; Marchiq, I.; Naiken, T.; Ilc, K.; Murray, C.M.; Critchlow, S.E.; Roux, D.; Simon, M.P.; Pouysségur, J. CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Proc. Natl. Acad. Sci. USA, 2011, 108(40), 16663-16668.
[http://dx.doi.org/10.1073/pnas.1106123108] [PMID: 21930917]
[67]
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]
[68]
Benjamin, D.; Robay, D.; Hindupur, S.K.; Pohlmann, J.; Colombi, M.; El-Shemerly, M.Y.; Maira, S.M.; Moroni, C.; Lane, H.A.; Hall, M.N. Dual inhibition of the lactate transporters MCT1 and MCT4 is synthetic lethal with metformin due to NAD+ depletion in cancer cells. Cell Rep., 2018, 25(11), 3047-3058.
[http://dx.doi.org/10.1016/j.celrep.2018.11.043] [PMID: 30540938]
[69]
Zhao, Z.; Wu, M.S.; Zou, C.; Tang, Q.; Lu, J.; Liu, D.; Wu, Y.; Yin, J.; Xie, X.; Shen, J.; Kang, T.; Wang, J. Downregulation of MCT1 inhibits tumor growth, metastasis and enhances chemotherapeutic efficacy in osteosarcoma through regulation of the NF-κB pathway. Cancer Lett., 2014, 342(1), 150-158.
[http://dx.doi.org/10.1016/j.canlet.2013.08.042] [PMID: 24012639]
[70]
Monti, D.; Sotgia, F.; Whitaker-Menezes, D.; Tuluc, M.; Birbe, R.; Berger, A.; Lazar, M.; Cotzia, P.; Draganova-Tacheva, R.; Lin, Z.; Domingo-Vidal, M.; Newberg, A.; Lisanti, M.P.; Martinez-Outschoorn, U. Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in breast cancer. Semin. Oncol., 2017, 44(3), 226-232.
[http://dx.doi.org/10.1053/j.seminoncol.2017.10.001] [PMID: 29248134]
[71]
Feichtinger, R.G.; Lang, R. Targeting L-Lactate metabolism to overcome resistance to immune therapy of melanoma and other tumor entities. J. Oncol., 2019, 2019, 2084195.
[http://dx.doi.org/10.1155/2019/2084195] [PMID: 31781212]
[72]
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]

Rights & Permissions Print Cite
Article Metrics
40
1
© 2024 Bentham Science Publishers | Privacy Policy