L-type amino acid transporter 1 | SLC7 family | IUPHAR/BPS Guide to PHARMACOLOGY

L-type amino acid transporter 1

Target id: 896

Nomenclature: L-type amino acid transporter 1

Abbreviated Name: LAT1

Systematic Nomenclature: SLC7A5

Family: SLC7 family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     L-type amino acid transporter 1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - SLC7A5 solute carrier family 7 member 5
Mouse - - Slc7a5 solute carrier family 7 (cationic amino acid transporter, y+ system), member 5
Rat - - Slc7a5 solute carrier family 7 member 5
Previous and Unofficial Names
4F2 light chain | 4F2LC | integral membrane protein E16 | Large neutral amino acids transporter small subunit 1 | CD98 | MPE16 | solute carrier family 7 (amino acid transporter light chain, L system), member 5 | TA1 | solute carrier family 7 member 5 | tumor-associated protein 1 | solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 | solute carrier family 7 (cationic amino acid transporter
Database Links
Specialist databases
Bioparadigms SLC Tables SLC7A5 (Hs)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
KYT-0353 Hs Inhibition - - 12
[12]
Immunopharmacology Comments
LAT1 has been identified as being a key transporter of the essential amino acids [3] that are required to support the nutritional demands of activated human T cells when mounting an immune response, and LAT1 expression is upregulated to meet this demand [2,11,16]. These findings suggest LAT1 as a novel target for the development of drugs with immuno-suppressive potential.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0050900 leukocyte migration TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0050900 leukocyte migration TAS
General Comments
LAT1 is a key transporter of essential amino acids [3]. LAT1 is used by many types of cancer cells to meet their high nutritional requirements [4,9]. Consequently, LAT1 inhbitors that would functionally starve cancers of essential nutrients, are being designed as potential anti-cancer therapeutics [1,5,7-8,10], and as adjuncts which enhance the efficacy of conventional chemotherapeutics [17]. LAT1 expression on cancer cells is also being used to target anti-cancer drugs to tumours using so-called 'LAT1-utilizing prodrugs' [6,14], and of particular clinical interest is the ability of some of these prodrugs to cross the blood-brain-barrier and the benefit this could bring to the treatment of brain tumours [13,15].

References

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1. Hayashi K, Anzai N. (2017) Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment. World J Gastrointest Oncol, 9 (1): 21-29. [PMID:28144396]

2. Hayashi K, Jutabha P, Endou H, Sagara H, Anzai N. (2013) LAT1 is a critical transporter of essential amino acids for immune reactions in activated human T cells. J. Immunol., 191 (8): 4080-5. [PMID:24038088]

3. Hayashi K, Jutabha P, Kamai T, Endou H, Anzai N. (2014) LAT1 is a central transporter of essential amino acids in human umbilical vein endothelial cells. J. Pharmacol. Sci., 124 (4): 511-3. [PMID:24671056]

4. Hayashi K, Jutabha P, Maeda S, Supak Y, Ouchi M, Endou H, Fujita T, Chida M, Anzai N. (2016) LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells. J. Pharmacol. Sci., 132 (3): 201-204. [PMID:27567475]

5. Huttunen KM, Gynther M, Huttunen J, Puris E, Spicer JA, Denny WA. (2016) A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. J. Med. Chem., 59 (12): 5740-51. [PMID:27253989]

6. Huttunen KM, Huttunen J, Aufderhaar I, Gynther M, Denny WA, Spicer JA. (2016) L-Type amino acid transporter 1 (lat1)-mediated targeted delivery of perforin inhibitors. Int J Pharm, 498 (1-2): 205-16. [PMID:26705152]

7. Imai H, Kaira K, Oriuchi N, Shimizu K, Tominaga H, Yanagitani N, Sunaga N, Ishizuka T, Nagamori S, Promchan K et al.. (2010) Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer. Anticancer Res., 30 (12): 4819-28. [PMID:21187458]

8. Kongpracha P, Nagamori S, Wiriyasermkul P, Tanaka Y, Kaneda K, Okuda S, Ohgaki R, Kanai Y. (2017) Structure-activity relationship of a novel series of inhibitors for cancer type transporter L-type amino acid transporter 1 (LAT1). J. Pharmacol. Sci., 133 (2): 96-102. [PMID:28242177]

9. Marshall AD, van Geldermalsen M, Otte NJ, Anderson LA, Lum T, Vellozzi MA, Zhang BK, Thoeng A, Wang Q, Rasko JE et al.. (2016) LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma. Int. J. Cancer, 139 (11): 2529-39. [PMID:27486861]

10. Napolitano L, Scalise M, Koyioni M, Koutentis P, Catto M, Eberini I, Parravicini C, Palazzolo L, Pisani L, Galluccio M et al.. (2017) Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs. Biochem. Pharmacol., 143: 39-52. [PMID:28709952]

11. Nii T, Segawa H, Taketani Y, Tani Y, Ohkido M, Kishida S, Ito M, Endou H, Kanai Y, Takeda E et al.. (2001) Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation. Biochem. J., 358 (Pt 3): 693-704. [PMID:11535130]

12. Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y et al.. (2010) L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci., 101 (1): 173-9. [PMID:19900191]

13. Papin-Michault C, Bonnetaud C, Dufour M, Almairac F, Coutts M, Patouraux S, Virolle T, Darcourt J, Burel-Vandenbos F. (2016) Study of LAT1 Expression in Brain Metastases: Towards a Better Understanding of the Results of Positron Emission Tomography Using Amino Acid Tracers. PLoS ONE, 11 (6): e0157139. [PMID:27276226]

14. Park K. (2017) Insight into brain-targeted drug delivery via LAT1-utilizing prodrugs. J Control Release, 261: 368. [PMID:28780138]

15. Puris E, Gynther M, Huttunen J, Petsalo A, Huttunen KM. (2017) L-type amino acid transporter 1 utilizing prodrugs: How to achieve effective brain delivery and low systemic exposure of drugs. J Control Release, 261: 93-104. [PMID:28662899]

16. Ren W, Liu G, Yin J, Tan B, Wu G, Bazer FW, Peng Y, Yin Y. (2017) Amino-acid transporters in T-cell activation and differentiation. Cell Death Dis, 8 (3): e2655. [PMID:28252650]

17. Yamauchi K, Sakurai H, Kimura T, Wiriyasermkul P, Nagamori S, Kanai Y, Kohno N. (2009) System L amino acid transporter inhibitor enhances anti-tumor activity of cisplatin in a head and neck squamous cell carcinoma cell line. Cancer Lett., 276 (1): 95-101. [PMID:19058911]

How to cite this page

SLC7 family: L-type amino acid transporter 1. Last modified on 30/05/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=896.