L-type amino acid transporter 1 | SLC7 family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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L-type amino acid transporter 1

  Target has curated data in GtoImmuPdb

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

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
ChEMBL Target
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 Value Parameter 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 22/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=896.