Glutamine transport and mitochondrial metabolism in cancer cell growth

Frontiers in Oncology

Volumn 7, Issue DEC, 2017, Pages

  Scalise, Mariafrancesca ^a   Pochini, Lorena ^a   Galluccio, Michele ^a   Console, Lara ^a   Indiveri, Cesare ^a,b  

^a UNIVERSITY OF CALABRIA   (Italy)

^b CNR   (Italy)

Author keywords

Drug design; Metabolism; Mitochondria; Plasma membrane; Proteoliposome; Tumors

Indexed keywords

ADENOSINE TRIPHOSPHATE; ASCT2 PROTEIN; CD98 ANTIGEN; GLUTAMIC ACID; GLUTAMINASE; GLUTATHIONE; LAT1 PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MEMBRANE PROTEIN; MICRORNA; MICRORNA 23A; NICOTINAMIDE ADENINE DINUCLEOTIDE; OXOGLUTARIC ACID; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; UNCLASSIFIED DRUG;

AMINO ACID TRANSPORT; CANCER GROWTH; CANCER THERAPY; CELL VIABILITY; ENERGY METABOLISM; FATTY ACID SYNTHESIS; GENE OVEREXPRESSION; GLUTAMINE TRANSPORT; HOMEOSTASIS; HUMAN; INTRACELLULAR SIGNALING; MITOCHONDRIAL RESPIRATION; NONHUMAN; OXIDATION REDUCTION POTENTIAL; PROTEIN LOCALIZATION; SHORT SURVEY;

EID: 85038036739     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2017.00306     Document Type: Short Survey

References (97)

1. Robey RB, Weisz J, Kuemmerle NB, Salzberg AC, Berg A, Brown DG, et al. Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis? Carcinogenesis (2015) 36(Suppl 1):S203-31. doi:10.1093/carcin/bgv037
2. Icard P, Lincet H. A global view of the biochemical pathways involved in the regulation of the metabolism of cancer cells. Biochim Biophys Acta (2012) 1826(2):423-33. doi:10.1016/j.bbcan.2012.07.001
3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144(5):646-74. doi:10.1016/j.cell.2011.02.013
4. Wisnovsky S, Lei EK, Jean SR, Kelley SO. Mitochondrial chemical biology: new probes elucidate the secrets of the powerhouse of the cell. Cell Chem Biol (2016) 23(8):917-27. doi:10.1016/j.chembiol.2016.06.012
5. Lleonart ME, Grodzicki R, Graifer DM, Lyakhovich A. Mitochondrial dysfunction and potential anticancer therapy. Med Res Rev (2017) 37(6):1275-98. doi:10.1002/med.21459
6. Cynober LA. Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition (2002) 18(9):761-6. doi:10.1016/S0899-9007(02)00780-3
7. Altman BJ, Stine ZE, Dang CV. From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer (2016) 16(10):619-34. doi:10.1038/nrc.2016.71
8. Zhang J, Pavlova NN, Thompson CB. Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine. EMBO J (2017) 36(10):1302-15. doi:10.15252/embj.201696151
9. Tardito S, Oudin A, Ahmed SU, Fack F, Keunen O, Zheng L, et al. Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nat Cell Biol (2015) 17(12):1556-68. doi:10.1038/ncb3272
10. Curi R, Lagranha CJ, Doi SQ, Sellitti DF, Procopio J, Pithon-Curi TC, et al. Molecular mechanisms of glutamine action. J Cell Physiol (2005) 204(2):392-401. doi:10.1002/jcp.20339
11. Scalise M, Pochini L, Galluccio M, Indiveri C. Glutamine transport. From energy supply to sensing and beyond. Biochim Biophys Acta (2016) 1857(8):1147-57. doi:10.1016/j.bbabio.2016.03.006
12. Cacace A, Sboarina M, Vazeille T, Sonveaux P. Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism. Oncogene (2017) 36(15):2074-84. doi:10.1038/onc.2016.364
13. Bode BP. Recent molecular advances in mammalian glutamine transport. J Nutr (2001) 131(9 Suppl):2475S-85S
14. Pochini L, Scalise M, Galluccio M, Indiveri C. Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Front Chem (2014) 2:61. doi:10.3389/fchem.2014.00061
15. Bhutia YD, Ganapathy V. Glutamine transporters in mammalian cells and their functions in physiology and cancer. Biochim Biophys Acta (2016) 1863(10):2531-9. doi:10.1016/j.bbamcr.2015.12.017
16. Fuchs BC, Bode BP. Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol (2005) 15(4):254-66. doi:10.1016/j.semcancer.2005.04.005
17. Broer S, Broer A. Amino acid homeostasis and signalling in mammalian cells and organisms. Biochem J (2017) 474(12):1935-63. doi:10.1042/BCJ20160822
18. Chiotellis A, Muller A, Weyermann K, Leutwiler DS, Schibli R, Ametamey SM, et al. Synthesis and preliminary biological evaluation of O-2((2-[(18)F]fluoroethyl)methylamino)ethyltyrosine ([(18)F]FEMAET) as a potential cationic amino acid PET tracer for tumor imaging. Amino Acids (2014) 46(8):1947-59. doi:10.1007/s00726-014-1754-7
19. Wang Q, Hardie RA, Hoy AJ, van Geldermalsen M, Gao D, Fazli L, et al. Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development. J Pathol (2015) 236(3):278-89. doi:10.1002/path.4518
20. Xu M, Sakamoto S, Matsushima J, Kimura T, Ueda T, Mizokami A, et al. Up-regulation of LAT1 during antiandrogen therapy contributes to progression in prostate cancer cells. J Urol (2016) 195(5):1588-97. doi:10.1016/j.juro.2015.11.071
21. Yanagisawa N, Satoh T, Hana K, Ichinoe M, Nakada N, Endou H, et al. l-amino acid transporter 1 may be a prognostic marker for local progression of prostatic cancer under expectant management. Cancer Biomark (2015) 15(4):365-74. doi:10.3233/CBM-150486
22. Wang Q, Bailey CG, Ng C, Tiffen J, Thoeng A, Minhas V, et al. Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression. Cancer Res (2011) 71(24):7525-36. doi:10.1158/0008-5472.CAN-11-1821
23. Gupta N, Miyauchi S, Martindale RG, Herdman AV, Podolsky R, Miyake K, et al. Upregulation of the amino acid transporter ATB0,+ (SLC6A14) in colorectal cancer and metastasis in humans. Biochim Biophys Acta (2005) 1741(1-2):215-23. doi:10.1016/j.bbadis.2005.04.002
24. Hassanein M, Qian J, Hoeksema MD, Wang J, Jacobovitz M, Ji X, et al. Targeting SLC1a5-mediated glutamine dependence in non-small cell lung cancer. Int J Cancer (2015) 137(7):1587-97. doi:10.1002/ijc.29535
25. Babu E, Bhutia YD, Ramachandran S, Gnanaprakasam JP, Prasad PD, Thangaraju M, et al. Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer. Biochem J (2015) 469(1):17-23. doi:10.1042/BJ20150437
26. McCracken AN, Edinger AL. Targeting cancer metabolism at the plasma membrane by limiting amino acid access through SLC6A14. Biochem J (2015) 470(3):e17-9. doi:10.1042/BJ20150721
27. van Geldermalsen M, Wang Q, Nagarajah R, Marshall AD, Thoeng A, Gao D, et al. ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene (2016) 35(24):3201-8. doi:10.1038/onc.2015.381
28. Li L, Di X, Wu M, Sun Z, Zhong L, Wang Y, et al. Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: toward a novel active targeting strategy in breast cancer therapy. Nanomedicine (2017) 13(3):987-98. doi:10.1016/j.nano.2016.11.012
29. Li L, Di X, Zhang S, Kan Q, Liu H, Lu T, et al. Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting. Colloids Surf B Biointerfaces (2016) 141:260-7. doi:10.1016/j.colsurfb.2016.01.041
30. Marshall AD, van Geldermalsen M, Otte NJ, Lum T, Vellozzi M, Thoeng A, et al. ASCT2 regulates glutamine uptake and cell growth in endometrial carcinoma. Oncogenesis (2017) 6(7):e367. doi:10.1038/oncsis.2017.70
31. Marshall AD, van Geldermalsen M, Otte NJ, Anderson LA, Lum T, Vellozzi MA, et al. LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma. Int J Cancer (2016) 139(11):2529-39. doi:10.1002/ijc.30371
32. Bjersand K, Seidal T, Sundstrom-Poromaa I, Akerud H, Skirnisdottir I. The clinical and prognostic correlation of HRNPM and SLC1A5 in pathogenesis and prognosis in epithelial ovarian cancer. PLoS One (2017) 12(6):e0179363. doi:10.1371/journal.pone.0179363
33. Liu Y, Yang L, An H, Chang Y, Zhang W, Zhu Y, et al. High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma. Sci Rep (2015) 5:16954. doi:10.1038/srep16954
34. Liu W, Chen H, Wong N, Haynes W, Baker CM, Wang X. Pseudohypoxia induced by miR-126 deactivation promotes migration and therapeutic resistance in renal cell carcinoma. Cancer Lett (2017) 394:65-75. doi:10.1016/j.canlet.2017.02.025
35. Coothankandaswamy V, Cao S, Xu Y, Prasad PD, Singh PK, Reynolds CP, et al. Amino acid transporter SLC6A14 is a novel and effective drug target for pancreatic cancer. Br J Pharmacol (2016) 173(23):3292-306. doi:10.1111/bph.13616
36. Penheiter AR, Erdogan S, Murphy SJ, Hart SN, Felipe Lima J, Rakhshan Rohakhtar F, et al. Transcriptomic and immunohistochemical profiling of SLC6A14 in pancreatic ductal adenocarcinoma. Biomed Res Int (2015) 2015:593572. doi:10.1155/2015/593572
37. Lu J, Chen M, Tao Z, Gao S, Li Y, Cao Y, et al. Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo. Oncotarget (2017) 8(44):76458-67. doi:10.18632/oncotarget.19479
38. Kasai N, Sasakawa A, Hosomi K, Poh TW, Chua BL, Yong WP, et al. Anti-tumor efficacy evaluation of a novel monoclonal antibody targeting neutral amino acid transporter ASCT2 using patient-derived xenograft mouse models of gastric cancer. Am J Transl Res (2017) 9(7):3399-410
39. Hayashi K, Anzai N. Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment. World J Gastrointest Oncol (2017) 9(1):21-9. doi:10.4251/wjgo.v9.i1.21
40. Wang J, Fei X, Wu W, Chen X, Su L, Zhu Z, et al. SLC7A5 functions as a downstream target modulated by CRKL in metastasis process of gastric cancer SGC-7901 cells. PLoS One (2016) 11(11):e0166147. doi:10.1371/journal.pone.0166147
41. Gupta N, Prasad PD, Ghamande S, Moore-Martin P, Herdman AV, Martindale RG, et al. Up-regulation of the amino acid transporter ATB(0,+) (SLC6A14) in carcinoma of the cervix. Gynecol Oncol (2006) 100(1):8-13. doi:10.1016/j.ygyno.2005.08.016
42. Broer A, Rahimi F, Broer S. Deletion of amino acid transporter ASCT2 (SLC1A5) reveals an essential role for transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to sustain glutaminolysis in cancer cells. J Biol Chem (2016) 291(25):13194-205. doi:10.1074/jbc.M115.700534
43. Cetindis M, Biegner T, Munz A, Teriete P, Reinert S, Grimm M. Glutaminolysis and carcinogenesis of oral squamous cell carcinoma. Eur Arch Otorhinolaryngol (2016) 273(2):495-503. doi:10.1007/s00405-015-3543-7
44. Honjo H, Kaira K, Miyazaki T, Yokobori T, Kanai Y, Nagamori S, et al. Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma. J Surg Oncol (2016) 113(4):381-9. doi:10.1002/jso.24160
45. Nikkuni O, Kaira K, Toyoda M, Shino M, Sakakura K, Takahashi K, et al. Expression of amino acid transporters (LAT1 and ASCT2) in patients with stage III/IV laryngeal squamous cell carcinoma. Pathol Oncol Res (2015) 21(4):1175-81. doi:10.1007/s12253-015-9954-3
46. Hayashi K, Jutabha P, Maeda S, Supak Y, Ouchi M, Endou H, et al. LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells. J Pharmacol Sci (2016) 132(3):201-4. doi:10.1016/j.jphs.2016.07.006
47. Shimizu A, Kaira K, Kato M, Yasuda M, Takahashi A, Tominaga H, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma. Melanoma Res (2015) 25(5):399-405. doi:10.1097/CMR.0000000000000181
48. Rosilio C, Nebout M, Imbert V, Griessinger E, Neffati Z, Benadiba J, et al. L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia. Leukemia (2015) 29(6):1253-66. doi:10.1038/leu.2014.338
49. Utsunomiya-Tate N, Endou H, Kanai Y. Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J Biol Chem (1996) 271(25):14883-90. doi:10.1074/jbc.271.25.14883
50. Scalise M, Pochini L, Pingitore P, Hedfalk K, Indiveri C. Cysteine is not a substrate but a specific modulator of human ASCT2 (SLC1A5) transporter. FEBS Lett (2015) 589(23):3617-23. doi:10.1016/j.febslet.2015.10.011
51. Bhutia YD, Babu E, Ramachandran S, Ganapathy V. Amino Acid transporters in cancer and their relevance to "glutamine addiction": novel targets for the design of a new class of anticancer drugs. Cancer Res (2015) 75(9):1782-8. doi:10.1158/0008-5472.CAN-14-3745
52. Zhu Y, Li T, Ramos da Silva S, Lee JJ, Lu C, Eoh H, et al. A critical role of glutamine and Asparagine gamma-nitrogen in nucleotide biosynthesis in cancer cells hijacked by an oncogenic virus. MBio (2017) 8(4):e1179-1117. doi:10.1128/mBio.01179-17
53. Toda K, Nishikawa G, Iwamoto M, Itatani Y, Takahashi R, Sakai Y, et al. Clinical role of ASCT2 (SLC1A5) in KRAS-mutated colorectal cancer. Int J Mol Sci (2017) 18(8):E1632. doi:10.3390/ijms18081632
54. Ratnikov B, Jeon YJ, Smith JW, Ronai ZA. Right on TARGET: glutamine metabolism in cancer. Oncoscience (2015) 2(8):681-3. doi:10.18632/oncoscience.205
55. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell (2009) 136(3):521-34. doi:10.1016/j.cell.2008.11.044
56. Scalise M, Pochini L, Panni S, Pingitore P, Hedfalk K, Indiveri C. Transport mechanism and regulatory properties of the human amino acid transporter ASCT2 (SLC1A5). Amino Acids (2014) 46(11):2463-75. doi:10.1007/s00726-014-1808-x
57. Pingitore P, Pochini L, Scalise M, Galluccio M, Hedfalk K, Indiveri C. Large scale production of the active human ASCT2 (SLC1A5) transporter in Pichia pastoris-functional and kinetic asymmetry revealed in proteoliposomes. Biochim Biophys Acta (2013) 1828(9):2238-46. doi:10.1016/j.bbamem.2013.05.034
58. Bi X, Henry CJ. Plasma-free amino acid profiles are predictors of cancer and diabetes development. Nutr Diabetes (2017) 7(3):e249. doi:10.1038/nutd.2016.55
59. Mastroberardino L, Spindler B, Pfeiffer R, Skelly PJ, Loffing J, Shoemaker CB, et al. Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature (1998) 395(6699):288-91. doi:10.1038/26246
60. Napolitano L, Scalise M, Galluccio M, Pochini L, Albanese LM, Indiveri C. LAT1 is the transport competent unit of the LAT1/CD98 heterodimeric amino acid transporter. Int J Biochem Cell Biol (2015) 67:25-33. doi:10.1016/j.biocel.2015.08.004
61. Tarlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell (2016) 167(6):1481.e-94.e. doi:10.1016/j.cell.2016.11.013
62. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell (2012) 149(2):274-93. doi:10.1016/j.cell.2012.03.017
63. Milkereit R, Persaud A, Vanoaica L, Guetg A, Verrey F, Rotin D. LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation. Nat Commun (2015) 6:7250. doi:10.1038/ncomms8250
64. Rebsamen M, Pochini L, Stasyk T, de Araujo ME, Galluccio M, Kandasamy RK, et al. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature (2015) 519(7544):477-81. doi:10.1038/nature14107
65. Wang S, Tsun ZY, Wolfson RL, Shen K, Wyant GA, Plovanich ME, et al. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science (2015) 347(6218):188-94. doi:10.1126/science.1257132
66. Pramod AB, Foster J, Carvelli L, Henry LK. SLC6 transporters: structure, function, regulation, disease association and therapeutics. Mol Aspects Med (2013) 34(2-3):197-219. doi:10.1016/j.mam.2012.07.002
67. Seow HF, Broer S, Broer A, Bailey CG, Potter SJ, Cavanaugh JA, et al. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat Genet (2004) 36(9):1003-7. doi:10.1038/ng1406
68. Broer S. The SLC38 family of sodium-amino acid co-transporters. Pflugers Arch (2014) 466(1):155-72. doi:10.1007/s00424-013-1393-y
69. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature (2012) 483(7391):603-7. doi:10.1038/nature11003
70. Gaglio D, Metallo CM, Gameiro PA, Hiller K, Danna LS, Balestrieri C, et al. Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol Syst Biol (2011) 7:523. doi:10.1038/msb.2011.56
71. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (2009) 324(5930):1029-33. doi:10.1126/science.1160809
72. Damiani C, Colombo R, Gaglio D, Mastroianni F, Pescini D, Westerhoff HV, et al. A metabolic core model elucidates how enhanced utilization of glucose and glutamine, with enhanced glutamine-dependent lactate production, promotes cancer cell growth: the WarburQ effect. PLoS Comput Biol (2017) 13(9):e1005758. doi:10.1371/journal.pcbi.1005758
73. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature (2011) 481(7381):380-4. doi:10.1038/nature10602
74. Jiang L, Shestov AA, Swain P, Yang C, Parker SJ, Wang QA, et al. Reductive carboxylation supports redox homeostasis during anchorage-independent growth. Nature (2016) 532(7598):255-8. doi:10.1038/nature17393
75. Maddocks OD, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, et al. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature (2013) 493(7433):542-6. doi:10.1038/nature11743
76. Alberghina L, Gaglio D, Gelfi C, Moresco RM, Mauri G, Bertolazzi P, et al. Cancer cell growth and survival as a system-level property sustained by enhanced glycolysis and mitochondrial metabolic remodeling. Front Physiol (2012) 3:362. doi:10.3389/fphys.2012.00362
77. Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature (2015) 520(7545):57-62. doi:10.1038/nature14344
78. Gaglio D, Soldati C, Vanoni M, Alberghina L, Chiaradonna F. Glutamine deprivation induces abortive s-phase rescued by deoxyribonucleotides in k-ras transformed fibroblasts. PLoS One (2009) 4(3):e4715. doi:10.1371/journal.pone.0004715
79. de la Rosa V, Campos-Sandoval JA, Martin-Rufian M, Cardona C, Mates JM, Segura JA, et al. A novel glutaminase isoform in mammalian tissues. Neurochem Int (2009) 55(1-3):76-84. doi:10.1016/j.neuint.2009.02.021
80. Katt WP, Cerione RA. Glutaminase regulation in cancer cells: a druggable chain of events. Drug Discov Today (2014) 19(4):450-7. doi:10.1016/j.drudis.2013.10.008
81. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature (2009) 458(7239):762-5. doi:10.1038/nature07823
82. Fung MKL, Chan GC. Drug-induced amino acid deprivation as strategy for cancer therapy. J Hematol Oncol (2017) 10(1):144. doi:10.1186/s13045-017-0509-9
83. Bak LK, Zieminska E, Waagepetersen HS, Schousboe A, Albrecht J. Metabolism of [U-13C]glutamine and [U-13C]glutamate in isolated rat brain mitochondria suggests functional phosphate-activated glutaminase activity in matrix. Neurochem Res (2008) 33(2):273-8. doi:10.1007/s11064-007-9471-1
84. Atlante A, Passarella S, Minervini GM, Quagliariello E. Glutamine transport in normal and acidotic rat kidney mitochondria. Arch Biochem Biophys (1994) 315(2):369-81. doi:10.1006/abbi.1994.1513
85. Indiveri C, Abruzzo G, Stipani I, Palmieri F. Identification and purification of the reconstitutively active glutamine carrier from rat kidney mitochondria. Biochem J (1998) 333(Pt 2):285-90. doi:10.1042/bj3330285
86. Sastrasinh S, Sastrasinh M. Glutamine transport in submitochondrial particles. Am J Physiol (1989) 257(6 Pt 2):F1050-8
87. Dejure FR, Royla N, Herold S, Kalb J, Walz S, Ade CP, et al. The MYC mRNA 3'-UTR couples RNA polymerase II function to glutamine and ribonucleotide levels. EMBO J (2017) 36(13):1854-68. doi:10.15252/embj.201796662
88. Cheng T, Sudderth J, Yang C, Mullen AR, Jin ES, Mates JM, et al. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci U S A (2011) 108(21):8674-9. doi:10.1073/pnas.1016627108
89. Katt WP, Lukey MJ, Cerione RA. A tale of two glutaminases: homologous enzymes with distinct roles in tumorigenesis. Future Med Chem (2017) 9(2):223-43. doi:10.4155/fmc-2016-0190
90. Giacomini KM, Huang SM. Transporters in drug development and clinical pharmacology. Clin Pharmacol Ther (2013) 94(1):3-9. doi:10.1038/clpt.2013.86
91. Colas C, Grewer C, Otte NJ, Gameiro A, Albers T, Singh K, et al. Ligand discovery for the alanine-serine-cysteine transporter (ASCT2, SLC1A5) from homology modeling and virtual screening. PLoS Comput Biol (2015) 11(10):e1004477. doi:10.1371/journal.pcbi.1004477
92. Costa M, Rosell A, Alvarez-Marimon E, Zorzano A, Fotiadis D, Palacin M. Expression of human heteromeric amino acid transporters in the yeast Pichia pastoris. Protein Expr Purif (2013) 87(1):35-40. doi:10.1016/j.pep.2012.10.003
93. Albers T, Marsiglia W, Thomas T, Gameiro A, Grewer C. Defining substrate and blocker activity of alanine-serine-cysteine transporter 2 (ASCT2) ligands with novel serine analogs. Mol Pharmacol (2012) 81(3):356-65. doi:10.1124/mol.111.075648
94. Augustyn E, Finke K, Zur AA, Hansen L, Heeren N, Chien HC, et al. LAT-1 activity of meta-substituted phenylalanine and tyrosine analogs. Bioorg Med Chem Lett (2016) 26(11):2616-21. doi:10.1016/j.bmcl.2016.04.023
95. Scalise M, Pochini L, Giangregorio N, Tonazzi A, Indiveri C. Proteoliposomes as tool for assaying membrane transporter functions and interactions with xenobiotics. Pharmaceutics (2013) 5(3):472-97. doi:10.3390/pharmaceutics5030472
96. Oppedisano F, Catto M, Koutentis PA, Nicolotti O, Pochini L, Koyioni M, et al. Inactivation of the glutamine/amino acid transporter ASCT2 by 1,2,3-dithiazoles: proteoliposomes as a tool to gain insights in the molecular mechanism of action and of antitumor activity. Toxicol Appl Pharmacol (2012) 265(1):93-102. doi:10.1016/j.taap.2012.09.011
97. Napolitano L, Scalise M, Koyioni M, Koutentis P, Catto M, Eberini I, et al. Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs. Biochem Pharmacol (2017) 143:39-52. doi:10.1016/j.bcp.2017.07.006