Nutrient transporters in cancer: Relevance to Warburg hypothesis and beyond

Pharmacology and Therapeutics

Volumn 121, Issue 1, 2009, Pages 29-40

  Ganapathy, Vadivel ^a   Thangaraju, Muthusamy ^a   Prasad, Puttur D ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

SLC16A1 (MCT1) SLC16A3 (MCT4); SLC2A1 (GLUT1) SLC5A1 (SGLT1); SLC5A8 (SMCT1); SLC6A14 (ATB0,+); SLC7A11 (xCT); SLC7A5 (LAT1)

Indexed keywords

4 N ACETYLDINALINE; 5 AZA 2' DEOXYCYTIDINE; AMINO ACID TRANSPORTER; APICIDIN; AZACITIDINE; BUTYRIC ACID; DEPSIPEPTIDE; DNA METHYLTRANSFERASE INHIBITOR; GLUCOSE TRANSPORTER; GLUCOSE TRANSPORTER 1; GLUTATHIONE; HISTONE DEACETYLASE INHIBITOR; LACTIC ACID; LACTIC ACID TRANSPORTER; MONOCARBOXYLATE TRANSPORTER 4; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; N METHYLTRYPTOPHAN; PROTEIN SLC3A2; PROTEIN SLC7A11; PROTEIN SLC7A5; PROTEIN SLCA14; PYRUVIC ACID; SODIUM GLUCOSE COTRANSPORTER 1; SODIUM MONOCARBOXYLATE TRANSPORTER 1; TRIBUTYRIN; UNCLASSIFIED DRUG; VORINOSTAT;

AMINO ACID TRANSPORT; APOPTOSIS; CANCER GROWTH; CANCER INHIBITION; CANCER THERAPY; DRUG TARGETING; GLUCOSE TRANSPORT; HUMAN; HYPOTHESIS; NEOPLASM; NONHUMAN; NUTRIENT AVAILABILITY; NUTRIENT UPTAKE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; TUMOR CELL;

AMINO ACID TRANSPORT SYSTEMS; ANIMALS; CATION TRANSPORT PROTEINS; CELL LINE, TUMOR; CELL PROLIFERATION; ENERGY METABOLISM; GLUCOSE; GLUCOSE TRANSPORT PROTEINS, FACILITATIVE; HUMANS; LACTIC ACID; MODELS, BIOLOGICAL; MONOCARBOXYLIC ACID TRANSPORTERS; NEOPLASMS;

EID: 57749111596     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2008.09.005     Document Type: Review

References (149)

1. Airley R.E., and Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy 53 (2007) 233-256
2. Baer S.C., Casaubon L., and Younes M. Expression of the human erythrocyte glucose transporter Glut1 in cutaneous neoplasia. J Am Acad Dermatol 37 (1997) 575-577
3. Baer S., Casaubon L., Schwartz M.R., Marcogliese A., and Younes M. Glut3 expression in biopsy specimens of laryngeal carcinoma is associated with poor survival. Laryngoscope 112 (2002) 393-396
4. Balinsky D., Platz C.E., and Lewis J.W. Isozyme patterns of normal, benign, and malignant human breast tissues. Cancer Res 43 (1983) 5895-5901
5. Barthel A., Okino S.T., Liao J., Nakatani K., Li J., and Whitlock Jr. J.P. Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J Biol Chem 274 (1999) 20281-20286
6. Bartrons R., and Caro J. Hypoxia, glucose metabolism and the Warburg's effect. J Bioenerg Biomembr 39 (2007) 223-229
7. Birnbaum M.J., Haspel H.C., and Rosen O.M. Transformation of rat fibroblasts by FSV rapidly increases glucose transporter gene transcription. Science 235 (1987) 1495-1498
8. Bode B.P., Fuchs B.C., Hurley B.P., Conroy J.L., Suetterlin J.E., and Tanabe K.K. Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cell lines. Am J Physiol Gastrointest Liver Physiol 283 (2002) G1062-G1073
9. Brandon M., Baldi P., and Wallace D.C. Mitochondrial mutations in cancer. Oncogene 25 (2006) 4647-4662
10. Bridges C.C., Hu H., Miyauchi S., Siddaramappa U.N., Ganapathy M.E., and Ignatowicz L. Induction of cystine/glutamate transporter xc- by human immunodeficiency virus type 1 transactivator protein Tat in retinal pigment epithelium. Invest Ophthalmol Vis Sci 45 (2004) 2906-2914
11. Broer S. The SLC6 orphans are forming a family of amino acid transporters. Neurochem Int 48 (2006) 559-567
12. Cantuaria G., Fagotti A., Ferrandina G., Magalhaes A., Nadji M., and Angioli R. GLUT-1 expression in ovarian carcinoma: association with survival and response to chemotherapy. Cancer 92 (2001) 1144-1150
13. Chandler J.D., Williams E.D., Slavin J.L., Best J.D., and Rogers S. Expression and localization of GLUT1 and GLUT12 in prostate carcinoma. Cancer 97 (2003) 2035-2042
14. Chen Z., Lu W., Garcia-Prieto C., and Huang P. The Warburg effect and its cancer therapeutic applications. J Bioenerg Biomembr 39 (2007) 267-274
15. Chesney J. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis. Curr Opin Clin Nutr Metab Care 9 (2006) 535-539
16. Chung W.J., Lyons S.A., Nelson G.M., Hamza H., Gladson C.L., and Gillespie G.Y. Inhibition of cystine uptake disrupts the growth of primary brain tumors. J Neurosci 25 (2005) 7101-7110
17. a+-monocarboxylate cotransporter. J Physiol 557 (2004) 719-731
18. Cook S.J., and Morley S.J. Nutrient-responsive mTOR signaling grows on Sterile ground. Biochem J 403 (2007) e1-e3
19. Dann S.G., and Thomas G. The amino acid sensitive TOR pathway from yeast to mammals. FEBS Lett 580 (2006) 2821-2829
20. DeBerardinis R.J., Mancuso A., Daikhin E., Nissim I., Yudkoff M., and Wehrli S. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104 (2007) 19345-19350
21. Dinndorf P.A., Gootenberg J., Cohen M.H., Keegan P., and Pazdur R. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist 12 (2007) 991-998
22. Dolinska M., Dybel A., Zablocka B., and Albrecht J. Glutamine transport in C6 glioma cells shows ASCT2 system characteristics. Neurochem Int 43 (2003) 501-507
23. Doxsee D.W., Gout P.W., Kurita T., Lo M., Buckley A.R., and Wang Y. Sulfasalazine-induced cystine starvation: potential use for prostate cancer therapy. Prostate 67 (2007) 162-171
24. Drummond D.C., Noble C.O., Kirpotin D.B., Guo Z., Scott G.K., and Benz C.C. Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 45 (2005) 495-528
25. Eberhard D.A., Giaccone G., Johnson B.E., and Non-Small-Cell Lung Cancer Working Group. Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting. J Clin Oncol 26 (2008) 983-994
26. Engelman J.A., and Cantley L.C. A sweet new role for EGFR in cancer. Cancer Cell 13 (2008) 375-376
27. Filomeni G., Rotilio G., and Ciriolo M.R. Cell signaling and the glutathione redox system. Biochem Pharmacol 64 (2002) 1057-1064
28. Flier J.S., Mueckler M.M., Usher P., and Lodisch H.F. Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 235 (1987) 1492-1495
29. Frank H., Groger N., Diener M., Becker C., Braun T., and Boettger T. Lactaturia and loss of sodium-dependent lactate uptake in the colon of SLC5A8-deficient mice. J Biol Chem 283 (2008) 24729-24737
30. Fuchs B.C., and Bode B.P. Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime?. Semin Cancer Biol 15 (2005) 254-266
31. Gallagher S.M., Castorino J.J., Wang D., and Philp N.J. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Res 67 (2007) 4182-4189
32. 0,+ as a delivery system for drugs and prodrugs. Curr Drug Targets Immune Endocr Metab Disord 5 (2005) 357-364
33. Ganapathy V., Gopal E., Miyauchi S., and Prasad P.D. Biological functions of SLC5A8, a candidate tumor suppressor. Biochem Soc Trans 33 (2005) 237-240
34. Ganapathy V., Gupta N., and Martindale R.G. In: Johnson L.R. (Ed). Protein digestion and absorption. In: Physiology of the Gastrointestinal Tract. 4th edition (2006), Raven Press, New York 1667-1692
35. Ganapathy V., Inoue K., Prasad P.D., and Ganapathy M.E. Cellular uptake of amino acids: system and regulation. In: Cynober L.A. (Ed). Metabolic and Therapeutic Aspects of Amino Acids in Clinical Nutrition. 2nd edition (2004), CRC Press, Boca Raton, FL 63-78
36. Ganapathy V., Thangaraju M., Gopal E., Itagaki S., Miyauchi S., and Prasad P.D. Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J 10 (2008) 193-199
37. Gopal E., Fei Y.J., Miyauchi M., Zhuang L., Prasad P.D., and Ganapathy V. Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family. Biochem J 388 (2005) 309-316
38. +-coupled transport of lactate. J Biol Chem 279 (2004) 44522-44532
39. Gopal E., Miyauchi S., Martin P.M., Ananth S., Roon P., and Smith S.B. Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract. Pharm Res 24 (2007) 575-584
40. Gopal E., Umapathy N.S., Martin P.M., Gnanaprakasam J.P., Becker H., and Wagner C.A. Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney. Biochim Biophys Acta 1768 (2007) 2690-2697
41. Gottlieb E., and Tomlinson I.P.M. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 5 (2005) 857-866
42. - cystine transporter: a new action for an old drug. Leukemia 15 (2001) 1633-1640
43. Gout P.W., Kang Y.J., Buckley D.J., Bruchovsky N., and Buckley A.R. Increased cystine uptake capability associated with malignant progression of Nb2 lymphoma cells. Leukemia 11 (1997) 1329-1337
44. 0,+ (SLC6A14) in colorectal cancer and metastasis in humans. Biochim Biophys Acta 1741 (2005) 215-223
45. Gupta N., Martin P.M., Prasad P.D., and Ganapathy V. SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor-suppressive function of the transporter. Life Sci 78 (2006) 2419-2425
46. 0,+ (SLC6A14) in carcinoma of the cervix. Gynecol Oncol 100 (2006) 8-13
47. Haber R.S., Rathan A., Weiser K.R., Pritsker A., Itzkowitz S.H., and Bodian C. GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer 83 (1998) 34-40
48. Halestrap A.P., and Meredith D. The SLC16 gene family - from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch - Eur J Physiol 447 (2004) 619-628
49. Harada N., Nagasaki A., Hata H., Matsuzaki H., Matsuno F., and Mitsuya H. Down-regulation of CD98 in melphalan-resistant myeloma cells with reduced drug uptake. Acta Haematol 103 (2000) 144-151
50. Higashi T., Tamaki N., Torizuka T., Nakamoto Y., Sakahara H., and Kimura T. FDG uptake, GLUT-1 glucose transporter and cellularity in human pancreatic tumors. J Nucl Med 39 (1998) 1727-1735
51. Hong C., Maunakea A., Jun P., Bollen A.W., Hodgson J.G., and Goldenberg D.D. Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8. Cancer Res 65 (2005) 3617-3623
52. Hoskin P.J., Sibtain A., Daley F.M., and Wilson G.D. GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. Br J Cancer 89 (2003) 1290-1297
53. Hu S., Liu D., Tufano R.P., Carson K.A., Rosenbaum E., and Cohen Y. Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer. Int J Cancer 119 (2006) 2322-2329
54. Iwanaga T., Takebe K., Kato I., Karaki S., and Kuwahara A. Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8. Biomed Res 27 (2006) 243-254
55. Kaleeba J.A., and Berger E.A. Kaposi's sarcoma-associated herpesvirus fusion-entry receptor: cystine transporter xCT. Science 311 (2006) 1921-1924
56. Kanai Y., and Hediger M.A. The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflugers Arch - Eur J Physiol 447 (2004) 469-479
57. Kang S.S., Chun Y.K., Hur M.H., Lee H.K., Kim Y.J., and Hong S.R. Clinical significance of glucose transporter 1 (GLUT1) expression in human breast carcinoma. Jpn J Cancer Res 93 (2002) 1123-1128
58. Karunakaran S., Umapathy N.S., Thangaraju M., Hatanaka T., Itagaki S., Munn D.H., et al. Interaction of tryptophan derivatives with SLC6A14 (ATB0,+) reveals the potential of the transporter as a drug target for cancer chemotherapy. Biochem J 414 (2008) 343-355
59. Kawamoto M. Breast cancer diagnosis by lactate dehydrogenase isozymes in nipple discharge. Cancer 73 (1994) 1836-1841
60. Kawauchi K., Araki K., Tobiume K., and Tanaka N. p53 regulates glucose metabolism through an IKK-NF-κB pathway and inhibits cell transformation. Nat Cell Biol 10 (2008) 611-618
61. Kim C.S., Cho S.H., Chun H.S., Lee S.Y., Endou H., and Kanai Y. BCH, an inhibitor of system L amino acid transporters, induces apoptosis in cancer cells. Biol Pharm Bull 31 (2008) 1096-1100
62. Kim D.K., Ahn S.G., Park J.C., Kanai Y., Endou H., and Yoon J.H. Expression of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in oral squamous cell carcinoma and its precursor lesions. Anticancer Res 24 (2004) 1671-1675
63. Kim J.W., Tchernyshyov I., Semenza G.L., and Dang C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3 (2006) 177-185
64. Kim J., and Dang C.V. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res 66 (2006) 8927-8930
65. Kim K., Kanai Y., Choi H.W., Tangtrongsup S., Chairoungdua A., and Babu E. Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells. Biochim Biophys Acta 1565 (2002) 112-121
66. Klatt P., and Lamas S. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Edur J Biochem 267 (2000) 4928-4944
67. Kobayashi K., Ohnishi A., Promsuk J., Shimizu S., Kanai Y., and Shiokawa Y. Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells. Neurosurgery 62 (2008) 493-504
68. Koukourakis M.I., Giatromanolaki A., Polychronidis A., Simopoulos C., Gatter K.C., and Harris A.L. Endogenous markers of hypoxia/anaerobic metabolism and anemia in primary colorectal cancer. Cancer Sci 97 (2006) 582-588
69. Koukourakis M.I., Giatromanolaki A., Simopoulos C., Polychronidis A., and Sivridis E. Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clin. Exp. Metastasis 22 (2005) 25-30
70. Koukourakis M.I., Giatromanolaki A., Harris A.L., and 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 66 (2006) 632-637
71. Lambert D.W., Wood I.S., Ellis A., and Shirazi-Beechey S.P. Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy. Br J Cancer 86 (2002) 1262-1269
72. Lastro M., Kourtidis A., Farley K., and Conklin D.S. xCT expression reduces the early cell cycle requirement for calcium signaling. Cell Signal 20 (2008) 390-399
73. Leiblich A., Cross S.S., Catto J.W.F., Phillips J.T., Leung H.Y., and Hamdy F.C. Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer. Oncogene 25 (2006) 2953-2960
74. Li H., Myeroff L., Smiraglia D., Romero M.F., Pretlow T.P., and Kasturi L. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci USA 100 (2003) 8412-8417
75. Li R., Younes M., Frolov A., Wheeler T.M., Scardino P., and Ohori M. Expression of neutral amino acid transporter ASCT2 in human prostate. Anticancer Res 23 (2003) 3413-3418
76. Lo M., Wang Y.Z., and Gout P.W. The xc- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases. J Cell Physiol 215 (2008) 593-602
77. Lyons S.A., Chung W.J., Weaver A.K., Ogunrinu T., and Sontheimer H. Autocrine glutamate signaling promotes glioma cell invasion. Cancer Res 67 (2007) 9463-9471
78. Macheda M.L., Rogers S., and Best J.D. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202 (2005) 654-662
79. Marks P., Rifkind R.A., Richon V.M., Breslow R., Miller T., and Kelly W.K. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 1 (2001) 194-202
80. Martin P.M., Gopal E., Ananth S., Zhuang L., Itagaki S., and Prasad B.M. Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain. J Neurochem 98 (2006) 279-288
81. Mazurek S., Boschek C.B., Hugo F., and Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15 (2005) 300-308
82. a+-coupled transporter for short-chain fatty acids. J Biol Chem 279 (2004) 13293-13296
83. Mori Y., Tsukinoki K., Yasuda M., Miyazawa M., Kaneko A., and Watanabe Y. Glucose transporter type 1 expression is associated with poor prognosis in patients with salivary gland tumors. Oral Oncol 43 (2007) 563-569
84. Mortensen P.B., and Clausen M.R. Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol 216 (1996) 132-148
85. Muller H.J., and Boos J. Use of L-asparaginase in childhood ALL. Crit Rev Oncol Hematol 28 (1998) 97-113
86. Murakami T., Nishiyama T., Shirotani T., Shinohara Y., Kan M., and Ishii K. Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes. J Biol Chem 267 (1992) 9300-9306
87. Nawashiro H., Otani N., Shinomiya N., Fukui S., Nomura N., and Yano A. The role of CD98 in astrocytic neoplasms. Hum Cell 15 (2002) 25-31
88. Ogawa J., Inoue H., and Koide S. Glucose transporter type 1 gene amplification correlates with sialyl-Lewis-X synthesis and proliferation in lung cancer. Int J Cancer 74 (1997) 189-192
89. Ohkame H., Masuda H., Ishii Y., and Kanai Y. Expression of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in liver tumor lesions of rat models. J Surg Oncol 78 (2001) 265-272
90. Osthus R.C., Shim H., Kim S., Li Q., Reddy R., and Mukherjee M. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem 275 (2000) 21797-21800
91. Palacin M., and Kanai Y. The ancillary proteins of HATs: SLC3 family of amino acid transporters. Pflugers Arch - Eur J Physiol 447 (2004) 490-494
92. Papandreou I., Cairns R.A., Fontana L., Lim A.L., and Denko N.C. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3 (2006) 187-197
93. Park J.Y., Helm J.F., Zheng W., Ly Q.P., Hodul P.J., and Centeno B.A. Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8 (SLC5A8) in human pancreatic cancer. Pancreas 36 (2008) e32-e39
94. Park J.Y., Zheng W., Kim D., Cheng J.Q., Kumar N., and Ahmad N. Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor. Cancer Detect Prev 31 (2007) 359-365
95. +/monocarboxylate transport (SMCT) protein expression correlates with survival in colon cancer: molecular characterization of SMCT. Proc Natl Acad Sci USA 103 (2006) 7270-7275
96. Pedersen P.L. The cancer cell's "power plants" as promising therapeutic targets: an overview. J Bioenerg Biomembr 39 (2007) 1-12
97. Phelps M.E. PET: the merging of biology and imaging into molecular imaging. J Nucl Med 41 (2000) 661-681
98. Pinheiro C., Longatto-Filho A., Scapulatempo C., Ferreira L., Martins S., and Pellerin L. Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch 452 (2008) 139-146
99. Pompella A., Corti A., Paolicchi A., Giommarelli C., and Zunino F. Gamma-glutamyltransferase, redox regulation and cancer drug resistance. Curr Opin Pharmacol 7 (2007) 360-366
100. Porra V., Ferraro-Peyret C., Durand C., Selmi-Ruby S., Giroud H., and Berger-Dutrieux N. Silencing of the tumor suppressor gene SLC5A8 is associated with BRAF mutations in classical papillary thyroid carcinomas. J Clin Endocrinol Metab 90 (2005) 3028-3035
101. Pouyssegur J., Dayan F., and Mazure N.M. Hypoxia signaling in cancer and approaches to enforce tumour regression. Nature 441 (2006) 437-443
102. Ratcliffe P.J. Fumarate hydratase deficiency and cancer: activation of hypoxia signaling?. Cancer Cell 11 (2007) 303-305
103. Rathmell J.C., Fox C.J., Plas D.R., Hammerman P.S., Cinalli R.M., and Thompson C.B. Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival. Mol Cell Biol 23 (2003) 7315-7328
104. Ravazoula P., Batistatou A., Aletra C., Ladopoulos J., Kourounis G., and Tzigounis B. Immunohistochemical expression of glucose transporter Glut 1 and cyclin D1 in breast carcinomas with negative lymph nodes. Eur J Gynaecol Oncol 24 (2003) 544-546
105. Reddy N.M., Kleeberger S.R., Bream J.H., Fallon P.G., Kensler T.W., Yamamoto M., et al. Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling. Oncogene 27 (2008) 5821-5832
106. Ristow M. Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metab Care 9 (2006) 339-345
107. Ritzhaupt A., Wood I.S., Ellis A., Hosie K.B., and Sirazi-Beechey S.P. Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate. J Physiol 513 (1998) 719-732
108. Rivenzon-Segal D., Boldin-Adamsky S., Seger D., Seger R., and Degani H. Glycolysis and glucose transporter 1 as markers of response to hormonal therapy in breast cancer. Int J Cancer 107 (2003) 177-182
109. Rodriguez A.M., Perron B., Lacroix L., Caillou B., Leblanc G., Schlumberger M., et al. Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes. J Clin Endocrinol Metab 87 (2002) 3500-3503
110. Rogers S., Docherty S.E., Slavin J.L., Henderson M.A., and Best J.D. Differential expression of GLUT12 in breast cancer and normal breast tissue. Cancer Lett 193 (2003) 225-233
111. Rudlowski C., Becker A.J., Schroder W., Rath W., Buttner R., and Moser M. GLUT1 messenger RNA and protein induction relates to the malignant transformation of cervical cancer. Am J Clin Pathol 120 (2003) 691-698
112. Schafer F.Q., and Buettner G.R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30 (2001) 1191-1212
113. Schagdarsurengin U., Gimm O., Dralle H., Hoang-Vu C., and Dammann R. CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma. Thyroid 16 (2006) 633-642
114. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3 (2003) 721-732
115. Semenza G.L. Hypoxia-inducible factor 1 (HIF-1) pathway (2007) Sci STKE 2007 (407), cm8
116. Semenza G.L. Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J 405 (2007) 1-9
117. Semenza G.L., Jiang B.H., Leung S.W., Passantino R., Concordet J.P., and Maire P. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271 (1996) 32529-32537
118. Shaw R.J. Glucose metabolism and cancer. Curr Opin Cell Biol 18 (2006) 598-608
119. Shennan D.B., Thomson J., Gow I.F., Travers M.T., and Barber M.C. L-Leucine transport in human breast cancer cells (MCF-7 and MDA-MB-231): kinetics, regulation by estrogen and molecular identity of the transporter. Biochim Biophys Acta 1664 (2004) 206-216
120. Singh R., Kaurya O.P., Shukla P.K., and Ramputty R. Lactate dehydrogenase (LDH) isoenzymes patterns in ocular tumours. Indian J. Ophthalmol 39 (1991) 44-47
121. 0,+. J Biol Chem 274 (1999) 23740-23745
122. Smith T.A. Facilitative glucose transporter expression in human cancer tissue. Br J Biomed Sci 56 (1999) 285-292
123. a+-coupled transporter for short-chain fatty acids (slc5a8) in the intestine and kidney of the mouse. Biomed Res 26 (2005) 213-221
124. Tamai S., Masuda H., Ishii Y., Suzuki S., Kanai Y., and Endou H. Expression of L-type amino acid transporter 1 in a rat model of liver metastasis: positive correlation with tumor size. Cancer Detect Prev 25 (2001) 439-445
125. Thangaraju M., Ananth S., Martin P.M., Roon P., Smith S.B., and Sterneck E. c/ebpδ null mouse as a model for the double-knockout of Slc5a8 and Slc5a12 in kidney. J Biol Chem 281 (2006) 26769-26773
126. Thangaraju, M., Carswell, K. N., Prasad, P. D., & Ganapathy, V. (in press). Colon cancer cells maintain low levels of pyruvate to avoid cell death caused by inhibition of HDAC1/HDAC3. Biochem J.
127. Thangaraju M., Cresci G., Itagaki S., Mellinger J., Browning D.D., Berger F.G., et al. Sodium-coupled transport of the short chain fatty acid butyrate by SLC5A8 and its relevance to colon cancer. J Gastrointest Surg 12 (2008) 1773-1781
128. Thangaraju M., Gopal E., Martin P.M., Ananth S., Smith S.B., and Prasad P.D. SLC5A8 triggers tumor cells apoptosis through pyruvate-dependent inhibition of histone deacetylases. Cancer Res 66 (2006) 11560-11564
129. Tohma T., Okazumi S., Makino H., Cho A., Mochizuki R., and Shuto K. Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis. Dis Esophagus 18 (2005) 185-189
130. Topping D.L., and Clifton P.M. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81 (2001) 1031-1064
131. Torres-Zamorano V., Leibach F.H., and Ganapathy V. Sodium-dependent homo- and hetero-exchange of neutral amino acids mediated by the amino acid transporter ATB0. Biochem Biophys Res Commun 245 (1998) 824-829
132. Tsukioka M., Matsumoto Y., Noriyuki M., Yoshida C., Nobeyama H., and Yoshida H. Expression of glucose transporters in epithelial ovarian carcinoma: correlation with clinical characteristics and tumor angiogenesis. Oncol Rep 18 (2007) 361-367
133. Uchino H., Kanai Y., Kim do K., Wempe M.F., Chairoungdua A., and Morimoto E. Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol 61 (2002) 729-737
134. Ueno M., Toyota M., Akino K., Suzuki H., Kusano M., and Satoh A. Aberrant methylation and histone deacetylation associated with silencing of SLC5A8 in gastric cancer. Tumour Biol 25 (2004) 134-140
135. Uldry M., and Thorens B. The SLC2 family of facilitated hexose and polyol transporters. Pflugers Arch - Eur J Physiol 447 (2004) 480-489
136. Ullah M.S., Davies A.J., and Halestrap A.P. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1α-dependent mechanism. J Biol Chem 281 (2006) 9030-9037
137. Verma N., Kumar K., Kaur G., and Anand S. L-Asparaginase: a promising chemotherapeutic agent. Crit Rev Biotechnol 27 (2007) 45-62
138. Verrey F., Closs E.I., Wagner C.A., Palacin M., Endou H., and Kanai Y. CATs and HATs: the SLC7 family of amino acid transporters. Pflugers Arch - Eur J Physiol 447 (2004) 532-542
139. Walenta S., and Mueller-Klieser W.F. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol 14 (2004) 267-274
140. Wallace D.C. Mitochondria and cancer: Warburg addressed. Cold Spring Harb Symp Quant Biol 70 (2005) 363-374
141. Wang X., and Proud C.G. The mTOR pathway in the control of protein synthesis. Physiology (Bethesda) 21 (2006) 362-369
142. Warburg O. The Metabolism of Tumours (1930), Constable, London
143. Warburg O. On the origin of cancer cells. Science 123 (1956) 309-314
144. Wasa M., Wang H.S., and Okada A. Characterization of l-glutamine transport by a human neuroblastoma cell line. Am J Physiol Cell Physiol 282 (2002) C1246-C1253
145. Weihua Z., Tsan R., Huang W.C., Wu Q., Chiu C.H., and Fidler I.J. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell 13 (2008) 385-393
146. Wilson M.C., Meredith D., Manning Fox J.E., Manoharan C., Davies A.J., and Halestrap A.P. 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 280 (2005) 27213-27221
147. Witte D., Ali N., Carlson N., and Younes M. Overexpression of the neutral amino acid transporter ASCT2 in human colorectal adenocarcinoma. Anticancer Res 22 (2002) 2555-2557
148. Wright E.M., and Turk E. The sodium/glucose cotransport family SLC5. Pflugers Arch - Eur J Physiol 447 (2004) 510-518
149. Younes M., Brown R.W., Mody D.R., Fernandez L., and Laucirica R. GLUT1 expression in human breast carcinoma: correlation with known prognostic markers. Anticancer Res 15 (1995) 2895-2898