SLC16A4

Summary

Gene Symbol: SLC16A4
Description: solute carrier family 16 member 4
Alias: MCT4, MCT5, monocarboxylate transporter 5, MCT 4, MCT 5, monocarboxylate transporter 4, solute carrier family 16 (monocarboxylic acid transporters), member 4, solute carrier family 16, member 4 (monocarboxylic acid transporter 5)
Species: human
Products:     SLC16A4

Top Publications

  1. Price N, Jackson V, Halestrap A. Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. Biochem J. 1998;329 ( Pt 2):321-8 pubmed
    ..and sequencing of four new full-length MCT-like sequences from human cDNA libraries, which we have denoted MCT3, MCT4, MCT5 and MCT6...
  2. Halestrap A, Meredith D. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch. 2004;447:619-28 pubmed
    The monocarboxylate cotransporter (MCT) family now comprises 14 members, of which only the first four (MCT1-MCT4) have been demonstrated experimentally to catalyse the proton-linked transport of metabolically important monocarboxylates ..
  3. Pinheiro C, Longatto Filho A, Scapulatempo C, Ferreira L, Martins S, Pellerin L, et al. Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch. 2008;452:139-46 pubmed publisher
    ..CRC samples (126 cases) were analyzed for MCT1, MCT2, and MCT4 immunoexpression and findings correlated with clinico-pathological parameters...
  4. Whitaker Menezes D, Martinez Outschoorn U, Lin Z, Ertel A, Flomenberg N, Witkiewicz A, et al. Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle. 2011;10:1772-83 pubmed
    ..A prediction of this hypothesis is that cancer-associated fibroblasts should express MCT4, a mono-carboxylate transporter that has been implicated in lactate efflux from glycolytic muscle fibers and ..
  5. Pértega Gomes N, Vizcaíno J, Miranda Gonçalves V, Pinheiro C, Silva J, Pereira H, et al. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer. 2011;11:312 pubmed publisher
    ..to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma...
  6. Pilegaard H, Terzis G, Halestrap A, Juel C. Distribution of the lactate/H+ transporter isoforms MCT1 and MCT4 in human skeletal muscle. Am J Physiol. 1999;276:E843-8 pubmed
    The profiles of the lactate/H+ transporter isoforms [monocarboxylate transporter isoforms (MCT)] MCT1 and MCT4 (formerly MCT3 of Price, N. T., V. N. Jackson, and A. P. Halestrap. Biochem. J...
  7. Ullah M, Davies A, Halestrap A. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem. 2006;281:9030-7 pubmed
    The monocarboxylate transporter MCT4 mediates lactic acid efflux from most tissues that are dependent on glycolysis for their ATP production...
  8. Gallagher S, Castorino J, Philp N. Interaction of monocarboxylate transporter 4 with beta1-integrin and its role in cell migration. Am J Physiol Cell Physiol. 2009;296:C414-21 pubmed publisher
    ..Using reciprocal coimmunoprecipitation assays, we found that beta(1)-integrin selectively associated with MCT4 in ARPE-19 and MDCK cells, two epithelial cell lines that express both MCT1 and MCT4...
  9. Pinheiro C, Reis R, 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;2010:427694 pubmed publisher
    ..In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44...

More Information

Publications107 found, 100 shown here

  1. Izumi H, Takahashi M, Uramoto H, Nakayama Y, Oyama T, Wang K, et al. Monocarboxylate transporters 1 and 4 are involved in the invasion activity of human lung cancer cells. Cancer Sci. 2011;102:1007-13 pubmed publisher
    ..We found that the expression of the monocarboxylate transporters MCT1 and MCT4, but not MCT5, in human lung cancer cell lines was significantly correlated with invasiveness...
  2. Meijer T, Schuurbiers O, Kaanders J, Looijen Salamon M, de Geus Oei L, Verhagen A, et al. Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4. Lung Cancer. 2012;76:316-23 pubmed publisher
    ..spatial distribution of the glycolysis and hypoxia related markers glucose transporter 1 (GLUT1) and monocarboxylate transporter 4 (MCT4) expression in relation to the vasculature in stage I, II and resectable stage IIIA NSCLC...
  3. Gerlinger M, Santos C, Spencer Dene B, Martinez P, Endesfelder D, BURRELL R, et al. Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target. J Pathol. 2012;227:146-56 pubmed publisher
    ..One of the most potent survival regulators, the monocarboxylate transporter MCT4 (SLC16A3), impaired ccRCC viability in all eight ccRCC lines tested and was the seventh most overexpressed gene in ..
  4. Halestrap A, Price N. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J. 1999;343 Pt 2:281-99 pubmed
    ..Direct demonstration of proton-linked lactate and pyruvate transport has been demonstrated for mammalian MCT1-MCT4, but only for MCT1 and MCT2 have detailed analyses of substrate and inhibitor kinetics been described following ..
  5. Kirk P, Wilson M, Heddle C, Brown M, Barclay A, Halestrap A. CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J. 2000;19:3896-904 pubmed
    ..co-immunoprecipitation and chemical cross-linking to demonstrate that CD147 specifically interacts with MCT1 and MCT4, two members of the proton-linked monocarboxylate (lactate) transporter family that play a fundamental role in ..
  6. Wilson M, Meredith D, Fox J, Manoharan C, Davies A, Halestrap A. Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70). J Biol Chem. 2005;280:27213-21 pubmed
    Translocation of monocarboxylate transporters MCT1 and MCT4 to the plasma membrane requires CD147 (basigin) with which they remain tightly associated. However, the importance of CD147 for MCT activity is unclear...
  7. Manning Fox J, Meredith D, Halestrap A. Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol. 2000;529 Pt 2:285-93 pubmed
    ..Here we report the characterisation of MCT4 expressed in Xenopus oocytes...
  8. Bickham D, Bentley D, Le Rossignol P, Cameron Smith D. The effects of short-term sprint training on MCT expression in moderately endurance-trained runners. Eur J Appl Physiol. 2006;96:636-43 pubmed
    ..the effects of short-term sprint training on transient changes in monocarboxylate lactate transporter 1 (MCT1) and MCT4 protein and mRNA content. Seven moderately endurance-trained runners (mean +/- SE; age 27.7+/-2...
  9. 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;27:557-69 pubmed publisher
    ..We evaluated CD147, monocarboxylate transporters (MCT1 and MCT4), and multidrug resistance (MDR) markers (MDR1 and MRP2) in 4 epithelial ovarian cancer (EOC) cell lines and ..
  10. Le Floch R, Chiche J, Marchiq I, Naïken T, Ilc K, Ilk K, et al. CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Proc Natl Acad Sci U S A. 2011;108:16663-8 pubmed publisher
    ..Lactic acid is mainly transported by two H(+)/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality...
  11. Curry J, Tuluc M, Whitaker Menezes D, Ames J, Anantharaman A, Butera A, et al. Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer. Cell Cycle. 2013;12:1371-84 pubmed publisher
    ..In addition, high oxidative stress (MCT4+) was very specific for cancer tissues...
  12. Weidmann C, Pomerleau J, Trudel Vandal L, Landreville S. Differential responses of choroidal melanocytes and uveal melanoma cells to low oxygen conditions. Mol Vis. 2017;23:103-115 pubmed
    ..dysregulated between the two oxygen concentrations; only the lactate transporter monocarboxylate transporter (MCT4) was statistically significantly upregulated at 3% O2...
  13. Kannen V, Garcia S, Silva W, Gasser M, Mönch R, Alho E, et al. Oncostatic effects of fluoxetine in experimental colon cancer models. Cell Signal. 2015;27:1781-8 pubmed publisher
    ..The gene expression of the MCT4 lactate transporter was significantly downregulated...
  14. Allen E, Miéville P, Warren C, Saghafinia S, Li L, Peng M, et al. Metabolic Symbiosis Enables Adaptive Resistance to Anti-angiogenic Therapy that Is Dependent on mTOR Signaling. Cell Rep. 2016;15:1144-60 pubmed publisher
    ..The glucose and lactate transporters GLUT1 and MCT4 are induced in distal hypoxic cells in a HIF1?-dependent fashion, indicative of glycolysis...
  15. Quanz M, Bender E, Kopitz C, Grünewald S, Schlicker A, Schwede W, et al. Preclinical Efficacy of the Novel Monocarboxylate Transporter 1 Inhibitor BAY-8002 and Associated Markers of Resistance. Mol Cancer Ther. 2018;17:2285-2296 pubmed publisher
    ..Associated markers of sensitivity were, among others, lack of MCT4 expression, low pleckstrin homology like domain family A member 2, and high pellino E3 ubiquitin protein ligase 1 ..
  16. Guan X, Bryniarski M, Morris M. In Vitro and In Vivo Efficacy of the Monocarboxylate Transporter 1 Inhibitor AR-C155858 in the Murine 4T1 Breast Cancer Tumor Model. AAPS J. 2018;21:3 pubmed publisher
    ..cancer (TNBC) characteristics and overexpression of MCT1 and CD147 (a MCT1 accessory protein), but absence of MCT4 expression...
  17. Urvalek A, Osei Sarfo K, Tang X, Zhang T, Scognamiglio T, Gudas L. Identification of Ethanol and 4-Nitroquinoline-1-Oxide Induced Epigenetic and Oxidative Stress Markers During Oral Cavity Carcinogenesis. Alcohol Clin Exp Res. 2015;39:1360-72 pubmed publisher
    ..Untr. tongue samples. 4-NQO/EtOH treatment also caused increases in markers of oxidative stress, including 4-HNE, MCT4/SLC16a3, and TOM20, as measured by immunohistochemistry...
  18. Khatami F, Payab M, Sarvari M, Gilany K, Larijani B, Arjmand B, et al. Oncometabolites as biomarkers in thyroid cancer: a systematic review. Cancer Manag Res. 2019;11:1829-1841 pubmed publisher
    ..glycosylation (immunoglobulin G [IgG] Fc-glycosylation), outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 4 (MCT4), choline, choline derivatives, myo-/scyllo-inositol, lactate, fatty acids, several amino acids, ..
  19. Schutkowski A, Wege N, Stangl G, König B. Tissue-specific expression of monocarboxylate transporters during fasting in mice. PLoS ONE. 2014;9:e112118 pubmed publisher
    ..Expression of MCT1, MCT2 and MCT10 was either increased or decreased by fasting dependent on the analyzed tissue. MCT4 and MCT8 were down-regulated by fasting in all examined tissues...
  20. Nunes A, Alves M, Tomás G, Conde V, Cristóvão A, Moreira P, et al. Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats. Br J Nutr. 2015;113:832-42 pubmed publisher
    ..evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined...
  21. Nath K, Guo L, Nancolas B, Nelson D, Shestov A, Lee S, et al. Mechanism of antineoplastic activity of lonidamine. Biochim Biophys Acta. 2016;1866:151-162 pubmed publisher
    ..5?M) and cooperatively inhibits l-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K0.5 and Hill coefficient values of 36-40?M and 1.65-1...
  22. Gu Z, Xia J, Xu H, Frech I, Tricot G, Zhan F. NEK2 Promotes Aerobic Glycolysis in Multiple Myeloma Through Regulating Splicing of Pyruvate Kinase. J Hematol Oncol. 2017;10:17 pubmed publisher
    ..NEK2 decreases the ratio of PKM2/PKM1 and also other aerobic glycolysis genes including GLUT4, HK2, ENO1, LDHA, and MCT4. Myeloma patients with high expression of NEK2 and PKM2 have lower event-free survival and overall survival...
  23. Wilde L, Roche M, Domingo Vidal M, Tanson K, Philp N, Curry J, et al. Metabolic coupling and the Reverse Warburg Effect in cancer: Implications for novel biomarker and anticancer agent development. Semin Oncol. 2017;44:198-203 pubmed publisher
    ..Monocarboxylate transporters (MCT) are critically necessary for release and uptake of these catabolites. MCT4 is involved in the release of monocarboxylates from cells, is regulated by catabolic transcription factors such as ..
  24. Rocha C, Martins A, Rato L, Silva B, Oliveira P, Alves M. Melatonin alters the glycolytic profile of Sertoli cells: implications for male fertility. Mol Hum Reprod. 2014;20:1067-76 pubmed publisher
    ..of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were determined by western blot. LDH activity was also assessed...
  25. Karthikeyan S, Potter J, Geschwind J, Sur S, Hamilton J, Vogelstein B, et al. Deregulation of energy metabolism promotes antifibrotic effects in human hepatic stellate cells and prevents liver fibrosis in a mouse model. Biochem Biophys Res Commun. 2016;469:463-9 pubmed publisher
    ..of glycolysis, as evident by elevated levels of lactate dehydrogenase, lactate production and its transporter, MCT4. Finally, the antifibrotic effects of 3-BrPA were validated in vivo in a mouse model of carbon tetrachloride-..
  26. Wagner W, Ciszewski W, Kania K. L- and D-lactate enhance DNA repair and modulate the resistance of cervical carcinoma cells to anticancer drugs via histone deacetylase inhibition and hydroxycarboxylic acid receptor 1 activation. Cell Commun Signal. 2015;13:36 pubmed publisher
    ..Moreover, HCAR1 shRNA-expressing cells produced significantly lower mRNA levels of monocarboxylate transporter 4. Finally, the enhancement of DNA repair and cell survival by lactate was suppressed by ..
  27. Meneses M, Bernardino R, Sa R, Silva J, Barros A, Sousa M, et al. Pioglitazone increases the glycolytic efficiency of human Sertoli cells with possible implications for spermatogenesis. Int J Biochem Cell Biol. 2016;79:52-60 pubmed publisher
    ..phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot...
  28. Tan Z, Xie N, Banerjee S, Cui H, Fu M, Thannickal V, et al. The monocarboxylate transporter 4 is required for glycolytic reprogramming and inflammatory response in macrophages. J Biol Chem. 2015;290:46-55 pubmed publisher
    ..to increased formation of intracellular lactate that is exported to the extracellular environment by monocarboxylate transporter 4 (MCT4)...
  29. Silva L, Goncalves L, Silva F, Domingues G, Máximo V, Ferreira J, et al. STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment. Tumour Biol. 2016;37:5385-95 pubmed publisher
    ..showed that SCC (SiHa) expresses MCT1 and is dependent on lactate to grow, whereas AC (HeLa) expresses MCT1 and MCT4, with higher growth capacities...
  30. 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;317:108-20 pubmed publisher
    ..73 ± 0.2 and contralateral 2.01 ± 0.4; MCT2 ipsilateral 2.1 ± 0.1; MCT4 ipsilateral 1.65 ± 0.1) and in the surrounding cortex of both the ipsilateral (MCT1 2.4 ± 0.4; MCT2 1...
  31. Dong J, Wang Y, Cui M, Wang X, Zheng W, Ma M, et al. Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and ?-Arrestin-1-Regulated Lactate Metabolism. Biol Psychiatry. 2017;81:654-670 pubmed publisher
    ..modulated monocarboxylate transporter 1 expression, ?-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a ?-arrestin-1/phospho-mitogen-activated protein ..
  32. Calgani A, Delle Monache S, Cesare P, Vicentini C, Bologna M, Angelucci A. Leptin contributes to long-term stabilization of HIF-1? in cancer cells subjected to oxygen limiting conditions. Cancer Lett. 2016;376:1-9 pubmed publisher
    ..effective in both low and high glycolytic cancer cell lines, and determined the up-regulation of lactate exporter MCT4 and its associated protein CD147...
  33. Rossi E, Bizzarro T, Granja S, Martini M, Capodimonti S, Luca E, et al. The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF V600E mutation. Endocrine. 2017;56:379-387 pubmed publisher
    ..The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to ..
  34. Futagi Y, Sasaki S, Kobayashi M, Narumi K, Furugen A, Iseki K. The flexible cytoplasmic loop 3 contributes to the substrate affinity of human monocarboxylate transporters. Biochim Biophys Acta Biomembr. 2017;1859:1790-1795 pubmed publisher
    ..Our study provides important insights into the structures and functions of hMCT1 and hMCT4 transporters. These findings contribute to the development of novel hMCT1 and/or hMCT4 inhibitors as anticancer agents. ..
  35. Adams T, Vail P, Ruiz A, Mollaee M, McCue P, Knudsen E, et al. Composite analysis of immunological and metabolic markers defines novel subtypes of triple negative breast cancer. Mod Pathol. 2017;: pubmed publisher
    ..Interestingly, a glycolytic tumor environment, as determined by the expression of MCT4 in the tumor stroma, was associated with the immune evasive environment and poor prognosis...
  36. Penheiter A, Deelchand D, Kittelson E, Damgard S, Murphy S, O Brien D, et al. Identification of a pyruvate-to-lactate signature in pancreatic intraductal papillary mucinous neoplasms. Pancreatology. 2018;18:46-53 pubmed publisher
    ..Strong expression of MCT4 and LDHA was observed by IHC in >90% of adenocarcinoma specimens...
  37. Millet G, Bentley D, Roels B, Mc Naughton L, Mercier J, Cameron Smith D. Effects of intermittent training on anaerobic performance and MCT transporters in athletes. PLoS ONE. 2014;9:e95092 pubmed publisher
    ..Biopsy samples from the vastus lateralis were analyzed for MCT1 and MCT4 using immuno-blotting techniques. The peak power output (PPO) increased (p<0.05) after training (7.2% and 6...
  38. Huang H, Mallidi S, Liu J, Chiang C, Mai Z, Goldschmidt R, et al. Photodynamic Therapy Synergizes with Irinotecan to Overcome Compensatory Mechanisms and Improve Treatment Outcomes in Pancreatic Cancer. Cancer Res. 2016;76:1066-77 pubmed publisher
    ..irinotecan treatment, we also demonstrate that irinotecan reduced the tumoral expression of monocarboxylate transporter 4, which was upregulated by PDT...
  39. Counillon L, Bouret Y, Marchiq I, Pouysségur J. Na(+)/H(+) antiporter (NHE1) and lactate/H(+) symporters (MCTs) in pH homeostasis and cancer metabolism. Biochim Biophys Acta. 2016;1863:2465-80 pubmed publisher
    The Na(+)/H(+)-exchanger NHE1 and the monocarboxylate transporters MCT1 and MCT4 are crucial for intracellular pH regulation, particularly under active metabolism...
  40. Battista M, Goetze K, Schmidt M, Cotarelo C, Weyer Elberich V, Hasenburg A, et al. Feasibility of induced metabolic bioluminescence imaging in advanced ovarian cancer patients: first results of a pilot study. J Cancer Res Clin Oncol. 2016;142:1909-16 pubmed publisher
    ..Furthermore, the expression of monocarboxylate transporters MCT1 and MCT4 was determined by immunofluorescence staining. 16 patients were screened, 12 entered the study...
  41. Morais Santos F, Granja S, Miranda Gonçalves V, Moreira A, Queirós S, Vilaça J, et al. Targeting lactate transport suppresses in vivo breast tumour growth. Oncotarget. 2015;6:19177-89 pubmed
    ..In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate ..
  42. Masur F, Benesch F, Pfannkuche H, Fuhrmann H, Gäbel G. Conjugated linoleic acids influence fatty acid metabolism in ovine ruminal epithelial cells. J Dairy Sci. 2016;99:3081-3095 pubmed publisher
    ..The expression of MCT1 mRNA increased after c9t11 and t10c12 treatment, and CLA c9t11 induced an upregulation of MCT4. Application of peroxisome proliferator-activated receptor (PPAR) α antagonist suggested that activation of PPAR..
  43. Voss D, Spina R, Carter D, Lim K, Jeffery C, Bar E. Disruption of the monocarboxylate transporter-4-basigin interaction inhibits the hypoxic response, proliferation, and tumor progression. Sci Rep. 2017;7:4292 pubmed publisher
    ..stem cells (GSCs) are enriched in the hypoxic tumor microenvironment, and that monocarboxylate transporter-4 (MCT4) is critical for mediating GSC signaling in hypoxia...
  44. Gustafsson H, Kale A, Daşu A, Lund A, Edqvist P, Roberg K. EPR Oximetry of Cetuximab-Treated Head-and-Neck Tumours in a Mouse Model. Cell Biochem Biophys. 2017;75:299-309 pubmed publisher
    ..resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1? were investigated by immunohistochemistry...
  45. Fisel P, Kruck S, Winter S, Bedke J, Hennenlotter J, Nies A, et al. DNA methylation of the SLC16A3 promoter regulates expression of the human lactate transporter MCT4 in renal cancer with consequences for clinical outcome. Clin Cancer Res. 2013;19:5170-81 pubmed publisher
    The monocarboxylate transporter 4 (MCT4) is a metabolic target in tumor biology because it mediates lactate transport across membranes resulting in antiapoptotic effects...
  46. Klier M, Andes F, Deitmer J, Becker H. Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters. J Biol Chem. 2014;289:2765-75 pubmed publisher
    ..It has previously been shown that transport activity of MCT1 and MCT4 is enhanced by the cytosolic carbonic anhydrase II (CAII) independent of its catalytic activity...
  47. Leon Swisher C, Koelsch B, Sukumar S, Sriram R, Santos R, Wang Z, et al. Dynamic UltraFast 2D EXchange SpectroscopY (UF-EXSY) of hyperpolarized substrates. J Magn Reson. 2015;257:102-9 pubmed publisher
    ..This new technique revealed decreased conversion of lactate-to-pyruvate with high expression of monocarboxylate transporter 4 (MCT4), known to correlate with aggressive cancer phenotypes...
  48. Rato L, Alves M, Duarte A, Santos M, Moreira P, Cavaco J, et al. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells. Int J Biochem Cell Biol. 2015;66:1-10 pubmed publisher
    ..production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency...
  49. Fisel P, Stühler V, Bedke J, Winter S, Rausch S, Hennenlotter J, et al. MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma. Oncotarget. 2015;6:30615-27 pubmed publisher
    ..mediating oncogenic processes partly through its role as binding partner for monocarboxylate transporter MCT4/SLC16A3...
  50. Horii N, Hasegawa N, Fujie S, Uchida M, Miyamoto Mikami E, Hashimoto T, et al. High-intensity intermittent exercise training with chlorella intake accelerates exercise performance and muscle glycolytic and oxidative capacity in rats. Am J Physiol Regul Integr Comp Physiol. 2017;312:R520-R528 pubmed publisher
    ..increased the maximal number of HIIE sessions and enhanced the expression of monocarboxylate transporter (MCT)1, MCT4, and peroxisome proliferator-activated receptor γ coactivator-1α concomitantly with the activities of lactate ..
  51. Wan W, Peng K, Li M, Qin L, Tong Z, Yan J, et al. Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α. Oncogene. 2017;36:3868-3877 pubmed publisher
    ..by decreasing the expression of genes participated in glucose metabolism, including GLUT1, HK2, PGK1, PGM, LDHA and MCT4. Mechanistically, JMJD1A cooperated with hypoxia inducible factor 1α (HIF1α), an important transcription ..
  52. Zhan K, Jiang M, Gong X, Zhao G. Effect of short-chain fatty acids on the expression of genes involved in short-chain fatty acid transporters and inflammatory response in goat jejunum epithelial cells. In Vitro Cell Dev Biol Anim. 2018;54:311-320 pubmed publisher
    ..05). The mRNA abundance of monocarboxylate transporter 1 (MCT1), MCT4, NHE1, and putative anion transporter 1 (PAT1) was elevated (p < 0...
  53. Bishop D, Edge J, Thomas C, Mercier J. High-intensity exercise acutely decreases the membrane content of MCT1 and MCT4 and buffer capacity in human skeletal muscle. J Appl Physiol (1985). 2007;102:616-21 pubmed
    ..High-intensity exercise was associated with a significant decrease in both MCT1 (-24%) and MCT4 (-26%) and a decrease in beta m(in vitro) (-11%; 135 +/- 3 to 120 +/- 2 micromol H+ x g dry muscle(-1) x pH(-1); P &..
  54. Fujii W, Kawahito Y, Nagahara H, Kukida Y, Seno T, Yamamoto A, et al. Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a novel therapeutic target for inflammatory arthritis. Arthritis Rheumatol. 2015;67:2888-96 pubmed publisher
    ..Finally, we examined the therapeutic effect of electrotransfer of monocarboxylate transporter 4 (MCT4)-specific siRNA into the articular synovium of mice with collagen-induced arthritis (CIA)...
  55. Ziegler K, Kerimi A, Poquet L, Williamson G. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4). Arch Biochem Biophys. 2016;599:3-12 pubmed publisher
    ..resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion...
  56. Luz M, Perez M, Azzalis L, Sousa L, Adami F, Fonseca F, et al. Evaluation of MCT1, MCT4 and CD147 Genes in Peripheral Blood Cells of Breast Cancer Patients and Their Potential Use as Diagnostic and Prognostic Markers. Int J Mol Sci. 2017;18: pubmed publisher
    ..The objective of this study was to verify the diagnostic and prognostic value of MCT1, MCT4 and CD147 in tumor and peripheral blood samples of patients with breast cancer undergoing chemotherapic ..
  57. Monti D, Sotgia F, Whitaker Menezes D, Tuluc M, Birbe R, Berger A, et al. Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer. Semin Oncol. 2017;44:226-232 pubmed publisher
    ..Histochemistry for the stromal metabolic markers monocarboxylate transporter 4 (MCT4) and caveolin-1 (CAV1) and the Ki67 proliferation assay and TUNEL apoptosis assay in carcinoma ..
  58. Zdralević M, Vucetic M, Daher B, Marchiq I, Parks S, Pouyssegur J. Disrupting the 'Warburg effect' re-routes cancer cells to OXPHOS offering a vulnerability point via 'ferroptosis'-induced cell death. Adv Biol Regul. 2018;68:55-63 pubmed publisher
    ..glucose-6-phosphate isomerase (GPI), lactate dehydrogenases (LDHA and B) and lactic acid transporters (MCT1, MCT4), we illuminate how cancer cells exploit metabolic plasticity to survive the metabolic and energetic blockade or ..
  59. Pinheiro C, Sousa B, Albergaria A, Paredes J, Dufloth R, Vieira D, et al. GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. Histol Histopathol. 2011;26:1279-86 pubmed publisher
    ..transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX) with the monocarboxylate transporters 1 (MCT1) and 4 (MCT4) and their chaperone, CD147, in breast cancer. The clinico-pathological value of GLUT1 and CAIX was also evaluated...
  60. Yan P, Li Y, Tang Z, Shu X, Liu X. High monocarboxylate transporter 4 protein expression in stromal cells predicts adverse survival in gastric cancer. Asian Pac J Cancer Prev. 2014;15:8923-9 pubmed
    Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC)...
  61. Pinheiro C, Granja S, Longatto Filho A, Faria A, Fragoso M, Lovisolo S, et al. GLUT1 expression in pediatric adrenocortical tumors: a promising candidate to predict clinical behavior. Oncotarget. 2017;8:63835-63845 pubmed publisher
    ..The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors.
  62. Bonen A, Miskovic D, Tonouchi M, Lemieux K, Wilson M, Marette A, et al. Abundance and subcellular distribution of MCT1 and MCT4 in heart and fast-twitch skeletal muscles. Am J Physiol Endocrinol Metab. 2000;278:E1067-77 pubmed
    The expression of two monocarboxylate transporters (MCTs) was examined in muscle and heart. MCT1 and MCT4 proteins are coexpressed in rat skeletal muscles, but only MCT1 is expressed in rat hearts...
  63. Vellonen K, Hakli M, Merezhinskaya N, Tervo T, Honkakoski P, Urtti A. Monocarboxylate transport in human corneal epithelium and cell lines. Eur J Pharm Sci. 2010;39:241-7 pubmed publisher
    ..The aim of the present study was to assess the expression and transporter role of human MCT1, MCT3 and MCT4 in the corneal epithelium, corneal epithelial cell lines (primary HCEpiC and immortalized HCE cells) and isolated ..
  64. Mogi A, Koga K, Aoki M, Hamasaki M, Uesugi N, Iwasaki A, et al. Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma. Virchows Arch. 2013;462:83-93 pubmed publisher
    ..Taken together, these results indicate that combined application of GLUT-1, MCT-1, and MCT-4 immunohistochemistry might be useful in differentiating MPM from RMH and suggest that MCT-1plays an important biological role. ..
  65. Choi S, Xue H, Wu R, Fazli L, Lin D, Collins C, et al. The MCT4 Gene: A Novel, Potential Target for Therapy of Advanced Prostate Cancer. Clin Cancer Res. 2016;22:2721-33 pubmed publisher
    ..Cellular lactic acid secretion is thought to be predominantly mediated by MCT4, a plasma membrane transporter protein...
  66. Nahm J, Kim H, Koo J. Glycolysis-related protein expression in thyroid cancer. Tumour Biol. 2017;39:1010428317695922 pubmed publisher
    ..We demonstrated that the expression levels of glycolysis-related proteins differ between thyroid cancer subtypes and are correlated with poorer prognosis, depending on the subtype. ..
  67. Mohr M, Nielsen T, Weihe P, Thomsen J, Aquino G, Krustrup P, et al. Muscle ion transporters and antioxidative proteins have different adaptive potential in arm than in leg skeletal muscle with exercise training. Physiol Rep. 2017;5: pubmed publisher
    ..Before training, monocarboxylate transporter 4 (MCT4), Na+/K+ pump α2, and superoxide dismutase 2 (SOD2) ..
  68. Lee Z, Teo X, Song Z, Nin D, Novera W, Choo B, et al. Intracellular Hyper-Acidification Potentiated by Hydrogen Sulfide Mediates Invasive and Therapy Resistant Cancer Cell Death. Front Pharmacol. 2017;8:763 pubmed publisher
    ..We demonstrated the utility of coupling GYY4137 with either simvastatin, known to inhibit monocarboxylate transporter 4 (MCT4), or metformin, to further boost glycolysis, in bringing about cell death for aggressive cancers...
  69. Pérez de Heredia F, Wood I, Trayhurn P. Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflugers Arch. 2010;459:509-18 pubmed publisher
    ..Screening by reverse transcription polymerase chain reaction indicated that the genes encoding MCT1, MCT2, and MCT4 are expressed in human adipose tissue, and in adipocytes and preadipocytes in culture...
  70. Doyen J, Trastour C, Ettore F, Peyrottes I, Toussant N, Gal J, et al. Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome. Biochem Biophys Res Commun. 2014;451:54-61 pubmed publisher
    ..Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR=0...
  71. Pelkonen L, Sato K, Reinisalo M, Kidron H, Tachikawa M, Watanabe M, et al. LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line. Mol Pharm. 2017;14:605-613 pubmed publisher
    ..PCFT was detected in both studied cell lines, but the expression was over 4-fold higher in hfRPE cells. MCT1, MCT4, MRP4, and Na+/K+ ATPase were upregulated in the ARPE19 cell line showing over 4-fold ..
  72. Gooptu M, Whitaker Menezes D, Sprandio J, Domingo Vidal M, Lin Z, Uppal G, et al. Mitochondrial and glycolytic metabolic compartmentalization in diffuse large B-cell lymphoma. Semin Oncol. 2017;44:204-217 pubmed publisher
    ..The lactate importer MCT4 is a marker of glycolysis, whereas the lactate importer MCT1 and TOMM20 are markers of OXPHOS metabolism...
  73. Mikkilineni L, Whitaker Menezes D, Domingo Vidal M, Sprandio J, Avena P, Cotzia P, et al. Hodgkin lymphoma: A complex metabolic ecosystem with glycolytic reprogramming of the tumor microenvironment. Semin Oncol. 2017;44:218-225 pubmed publisher
    ..translocase of the outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 1 (MCT1), and monocarboxylate transporter 4 (MCT4). TOMM20 is a marker of mitochondrial oxidative phosphorylation (OXPHOS) metabolism...
  74. Cao J, Ng M, Felmlee M. Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking. J Pharm Pharm Sci. 2017;20:435-444 pubmed publisher
    ..CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking...
  75. Green H, Halestrap A, Mockett C, O Toole D, Grant S, Ouyang J. Increases in muscle MCT are associated with reductions in muscle lactate after a single exercise session in humans. Am J Physiol Endocrinol Metab. 2002;282:E154-60 pubmed
    ..The single exercise session also resulted in elevations (P < 0.05) in the monocarboxylate transporters MCT1 and MCT4 throughout the 6 days after exercise...
  76. Settle P, Mynett K, Speake P, Champion E, Doughty I, Sibley C, et al. Polarized lactate transporter activity and expression in the syncytiotrophoblast of the term human placenta. Placenta. 2004;25:496-504 pubmed
    ..01 mm in MVM and BM respectively. Western blotting and immunolocalization examining the distribution of MCT1 and MCT4, showed that MCT expression was polarized, MCT1 being predominantly localized to BM and MCT4 showing greater ..
  77. Bishop D, Edge J, Thomas C, Mercier J. Effects of high-intensity training on muscle lactate transporters and postexercise recovery of muscle lactate and hydrogen ions in women. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1991-8 pubmed publisher
    ..Muscle samples were analyzed for ATP, phosphocreatine (PCr), lactate, and H+; MCT1 and MCT4 relative abundance and betam(in vitro) were also determined in resting muscle only...
  78. Kong S, Nøhr Nielsen A, Zeeberg K, Reshkin S, Hoffmann E, Novak I, et al. Monocarboxylate Transporters MCT1 and MCT4 Regulate Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells. Pancreas. 2016;45:1036-47 pubmed publisher
    ..The aim of this work was to explore the roles of H-lactate monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in PDAC cell migration and invasiveness...
  79. Bovenzi C, Hamilton J, Tassone P, Johnson J, Cognetti D, Luginbuhl A, et al. Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis. Biomed Res Int. 2015;2015:242437 pubmed publisher
    ..The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147...
  80. Viswanath P, Najac C, Izquierdo García J, Pankov A, Hong C, Eriksson P, et al. Mutant IDH1 expression is associated with down-regulation of monocarboxylate transporters. Oncotarget. 2016;7:34942-55 pubmed publisher
    ..This reduction was associated with lower expression of the monocarboxylate transporters MCT1 and MCT4 in NHAIDHmut cells...
  81. Ruan Y, Zeng F, Cheng Z, Zhao X, Fu P, Chen H. High expression of monocarboxylate transporter 4 predicts poor prognosis in patients with lung adenocarcinoma. Oncol Lett. 2017;14:5727-5734 pubmed publisher
    b>Monocarboxylate transporter 4 (MCT-4) serves a key function in transporting lactate across the plasma membrane in various types of human cancer...
  82. Tassone P, Domingo Vidal M, Whitaker Menezes D, Lin Z, Roche M, Tuluc M, et al. Metformin Effects on Metabolic Coupling and Tumor Growth in Oral Cavity Squamous Cell Carcinoma Coinjection Xenografts. Otolaryngol Head Neck Surg. 2017;:194599817746934 pubmed publisher
    ..coupled tumor compartments: a glycolytic stromal compartment with low caveolin-1 (CAV1) and high monocarboxylate transporter 4 (MCT4) expression and a highly proliferative carcinoma cell compartment with high MCT1...
  83. Py G, Lambert K, Perez Martin A, Raynaud E, Prefaut C, Mercier J. Impaired sarcolemmal vesicle lactate uptake and skeletal muscle MCT1 and MCT4 expression in obese Zucker rats. Am J Physiol Endocrinol Metab. 2001;281:E1308-15 pubmed
    ..1) the hindlimb muscle mass lactate uptake and 2) the expression of monocarboxylate transporter isoforms MCT1 and MCT4, as well as lactate dehydrogenase (LDH) isozyme distribution, in various skeletal muscles of Zucker fa/fa rats ..
  84. Becker H, Mohebbi N, Perna A, Ganapathy V, Capasso G, Wagner C. Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis. Am J Physiol Renal Physiol. 2010;299:F141-54 pubmed publisher
    ..CD147, a beta-subunit of MCT1 and MCT4, showed partially overlapping expression with MCT1 and MCT2. However, CD147 was also found in intercalated cells...
  85. Wang D, Wang Q, Yan G, Qiao Y, Sun L, Zhu B, et al. High glucose and interleukin 1β-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4. Biochem Biophys Res Commun. 2015;466:607-14 pubmed publisher
    ..Here, we evaluate the role of MCT4 in high glucose (HG) and interleukin 1β (IL-1β)-induced apoptosis in human umbilical vein endothelial cells (..
  86. Lee J, Lee I, Chang W, Ahn S, Lim S, Kim H, et al. MCT4 as a potential therapeutic target for metastatic gastric cancer with peritoneal carcinomatosis. Oncotarget. 2016;7:43492-43503 pubmed publisher
    ..In GC cell lines, MCT1, 2, and 4 were up-regulated with different expression levels; MCT1 and MCT4 were more widely expressed in GC cell lines compared with MCT2...
  87. Juel C, Holten M, Dela F. Effects of strength training on muscle lactate release and MCT1 and MCT4 content in healthy and type 2 diabetic humans. J Physiol. 2004;556:297-304 pubmed
    ..uptake rates, and it leaves the cells via simple diffusion and two monocarboxylate transporter proteins, MCT1 and MCT4. In response to endurance training MCT1 - and possibly MCT4 - content in muscle increases...
  88. Hilgendorf C, Ahlin G, Seithel A, Artursson P, Ungell A, Karlsson J. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos. 2007;35:1333-40 pubmed
    ..In the kidney, OAT1 was expressed at the highest levels, followed by OAT3, OAT4, MCT5, MDR1, MRP2, OCT2, and OCTN2...
  89. Gotanda Y, Akagi Y, Kawahara A, Kinugasa T, Yoshida T, Ryu Y, et al. Expression of monocarboxylate transporter (MCT)-4 in colorectal cancer and its role: MCT4 contributes to the growth of colorectal cancer with vascular endothelial growth factor. Anticancer Res. 2013;33:2941-7 pubmed
    ..b>MCT4 has also been reported to be involved in tumor growth and infiltration...
  90. Ohno A, Yorita K, Haruyama Y, Kondo K, Kato A, Ohtomo T, et al. Aberrant expression of monocarboxylate transporter 4 in tumour cells predicts an unfavourable outcome in patients with hepatocellular carcinoma. Liver Int. 2014;34:942-52 pubmed publisher
    ..determined the prognostic impact of infiltrating tumour-associated macrophages and the expression of monocarboxylate transporter 4 (MCT4) and glypican 3 (GPC3) in hepatocellular carcinoma (HCC) clinical specimens...
  91. Liu B, Niu L, Shen M, Gao L, Wang C, Li J, et al. Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy. Mol Neurobiol. 2014;50:327-38 pubmed publisher
    Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron population with metabolic intermediates to meet energy requirements under ..
  92. Gao H, Zhao M, Zhang Y, Zhou D, Xu L, Li G, et al. Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration. J Cancer Res Clin Oncol. 2015;141:1151-62 pubmed publisher
    b>Monocarboxylate transporter 4 (MCT4) is a critical component in the glycolytic metabolism of cancer cells, and is also important for malignant behavior...