{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T21:05:27Z","timestamp":1774991127180,"version":"3.50.1"},"reference-count":194,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NORTE-01-0247-FEDER-033399"],"award-info":[{"award-number":["NORTE-01-0247-FEDER-033399"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/114803\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/114803\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The role of the amino acid transporters ASCT2 and LAT1 in cancer has been explored throughout the years. In this review, we report their impact on the hallmarks of cancer, as well as their clinical significance. Overall, both proteins have been associated with cell death resistance through dysregulation of caspases and sustainment of proliferative signaling through mTOR activation. Furthermore, ASCT2 appears to play an important role in cellular energetics regulation, whereas LAT1 expression is associated with angiogenesis and invasion and metastasis activation. The molecular impact of these proteins on the hallmarks of cancer translates into various clinical applications and both transporters have been identified as prognostic factors in many types of cancer. Concerning their role as therapeutic targets, efforts have been undertaken to synthesize competitive or irreversible ASCT2 and LAT1 inhibitors. However, JHP203, a selective inhibitor of the latter, is, to the best of our knowledge, the only compound included in a Phase 1 clinical trial. In conclusion, considering the usefulness of ASCT2 and LAT1 in a variety of cancer-related pathways and cancer therapy\/diagnosis, the development and testing of novel inhibitors for these transporters that could be evaluated in clinical trials represents a promising approach to cancer prognosis improvement.<\/jats:p>","DOI":"10.3390\/cancers13020203","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T08:58:34Z","timestamp":1610096314000},"page":"203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-286X","authenticated-orcid":false,"given":"Catarina","family":"Lopes","sequence":"first","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Carina","family":"Pereira","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research, University of Porto, Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Research Department of the Portuguese League Against Cancer\u2014North (LPCC-NRNorte), Estrada da Circunvala\u00e7\u00e3o, 4200-177 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1042\/BCJ20160822","article-title":"Amino acid homeostasis and signalling in mammalian cells and organisms","volume":"474","year":"2017","journal-title":"Biochem. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.devcel.2016.02.012","article-title":"Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells","volume":"36","author":"Hosios","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.semcancer.2005.04.005","article-title":"Amino acid transporters ASCT2 and LAT1 in cancer: Partners in crime?","volume":"15","author":"Fuchs","year":"2005","journal-title":"Semin. Cancer Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1074\/jbc.RA118.006378","article-title":"Ablation of the ASCT2 (SLC1A5) gene encoding a neutral amino acid transporter reveals transporter plasticity and redundancy in cancer cells","volume":"294","author":"Rahimi","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.tibs.2018.05.003","article-title":"Amino acid transporters revisited: New views in health and disease","volume":"43","author":"Kandasamy","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2655","DOI":"10.1038\/cddis.2016.222","article-title":"Amino-acid transporters in T-cell activation and differentiation","volume":"8","author":"Ren","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-3-319-45096-4_8","article-title":"The glutamine transporters and their role in the glutamate\/GABA-glutamine Cycle","volume":"13","author":"Leke","year":"2016","journal-title":"Adv. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1152\/physrev.1990.70.1.43","article-title":"Role of amino acid transport and countertransport in nutrition and metabolism","volume":"70","author":"Christensen","year":"1990","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ejphar.2018.07.007","article-title":"The role of ASCT2 in cancer: A review","volume":"837","author":"Liu","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e48120","DOI":"10.7554\/eLife.48120","article-title":"Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation","volume":"8","author":"Yu","year":"2019","journal-title":"eLife"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.pharmthera.2008.09.005","article-title":"Nutrient transporters in cancer: Relevance to Warburg hypothesis and beyond","volume":"121","author":"Ganapathy","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Scalise, M., Pochini, L., Console, L., Pappacoda, G., Pingitore, P., Hedfalk, K., and Indiveri, C. (2018). Cys site-directed mutagenesis of the human SLC1A5 (ASCT2) transporter: Structure\/function relationships and crucial role of Cys467 for redox sensing and glutamine transport. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030648"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Scalise, M., Pochini, L., Console, L., Losso, M.A., and Indiveri, C. (2018). The human SLC1A5 (ASCT2) amino acid transporter: From function to structure and role in cell biology. Front. Cell Dev. Biol., 6.","DOI":"10.3389\/fcell.2018.00096"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1016\/j.febslet.2015.10.011","article-title":"Cysteine is not a substrate but a specific modulator of human ASCT2 (SLC1A5) transporter","volume":"589","author":"Scalise","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s41594-018-0076-y","article-title":"Cryo-EM structure of the human neutral amino acid transporter ASCT2","volume":"25","author":"Garaeva","year":"2018","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1107\/S2059798319009094","article-title":"LAT1 (SLC7A5) and CD98hc (SLC3A2) complex dynamics revealed by single-particle cryo-EM","volume":"75","author":"Chiduza","year":"2019","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.biocel.2015.08.004","article-title":"LAT1 is the transport competent unit of the LAT1\/CD98 heterodimeric amino acid transporter","volume":"67","author":"Napolitano","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0005-2736(01)00384-4","article-title":"Human L-type amino acid transporter 1 (LAT1): Characterization of function and expression in tumor cell lines","volume":"1514","author":"Yanagida","year":"2001","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5582\/irdr.2015.01024","article-title":"The role of L-type amino acid transporter 1 in human tumors","volume":"4","author":"Zhao","year":"2015","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23629","DOI":"10.1074\/jbc.273.37.23629","article-title":"Expression Cloning and Characterization of a Transporter for Large Neutral Amino Acids Activated by the Heavy Chain of 4F2 Antigen (CD98)","volume":"273","author":"Kanai","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7358","DOI":"10.1021\/acs.jmedchem.8b01007","article-title":"Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)","volume":"61","author":"Chien","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41594-019-0237-7","article-title":"Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc","volume":"26","author":"Lee","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Singh, N., and Ecker, G.F. (2018). Insights into the structure, function, and ligand discovery of the large neutral amino acid transporter 1, LAT1. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051278"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41586-019-1011-z","article-title":"Structure of the human LAT1\u20134F2hc heteromeric amino acid transporter complex","volume":"568","author":"Yan","year":"2019","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Scalise, M., Galluccio, M., Console, L., Pochini, L., and Indiveri, C. (2018). The human SLC7A5 (LAT1): The intriguing histidine\/large neutral amino acid transporter and its relevance to human health. Front. Chem., 6.","DOI":"10.3389\/fchem.2018.00243"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1440-1827.2011.02650.x","article-title":"High expression of L-type amino-acid transporter 1 (LAT1) in gastric carcinomas: Comparison with non-cancerous lesions","volume":"61","author":"Ichinoe","year":"2011","journal-title":"Pathol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16954","DOI":"10.1038\/srep16954","article-title":"High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma","volume":"5","author":"Liu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_29","first-page":"6006","article-title":"Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer","volume":"7","author":"Huang","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s11307-016-1008-z","article-title":"Non-invasive glutamine PET reflects pharmacological inhibition of BRAF(V600E) in vivo","volume":"19","author":"Schulte","year":"2017","journal-title":"Mol. Imaging Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e367","DOI":"10.1038\/oncsis.2017.70","article-title":"ASCT2 regulates glutamine uptake and cell growth in endometrial carcinoma","volume":"6","author":"Marshall","year":"2017","journal-title":"Oncogenesis"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Risinger, J., Allard, J., Chandran, U., Day, R., Chandramouli, G., Miller, C., Zahn, C., Oliver, J., Litzi, T., and Marcus, C. (2013). Gene expression analysis of early stage endometrial cancers reveals unique transcripts associated with grade and histology but not depth of invasion. Front. Oncol., 3.","DOI":"10.3389\/fonc.2013.00139"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"76458","DOI":"10.18632\/oncotarget.19479","article-title":"Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo","volume":"8","author":"Lu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sun, H.W., Yu, X.J., Wu, W.C., Chen, J., Shi, M., Zheng, L., and Xu, J. (2016). GLUT1 and ASCT2 as predictors for prognosis of hepatocellular carcinoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168907"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1038\/bjc.2014.88","article-title":"ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer","volume":"110","author":"Shimizu","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_36","first-page":"3725","article-title":"Clinical associations between ASCT2 and p-mTOR in the pathogenesis and prognosis of epithelial ovarian cancer","volume":"40","author":"Guo","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/his.12464","article-title":"Clinicopathological significance of ASC amino acid transporter-2 expression in pancreatic ductal carcinoma","volume":"66","author":"Kaira","year":"2015","journal-title":"Histopathology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/path.4518","article-title":"Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development","volume":"236","author":"Wang","year":"2015","journal-title":"J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1111\/hepr.12431","article-title":"Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma","volume":"45","author":"Namikawa","year":"2015","journal-title":"Hepatol. Res."},{"key":"ref_40","first-page":"1161","article-title":"Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in patients with ovarian tumors","volume":"7","author":"Kaira","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Papin-Michault, C., Bonnetaud, C., Dufour, M., Almairac, F., Coutts, M., Patouraux, S., Virolle, T., Darcourt, J., and 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.","DOI":"10.1371\/journal.pone.0157139"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Betsunoh, H., Fukuda, T., Anzai, N., Nishihara, D., Mizuno, T., Yuki, H., Masuda, A., Yamaguchi, Y., Abe, H., and Yashi, M. (2013). Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-509"},{"key":"ref_43","first-page":"7410","article-title":"L-type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer","volume":"14","author":"Hayase","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"152972","DOI":"10.1016\/j.prp.2020.152972","article-title":"Positive correlation of expression of L-type amino-acid transporter 1 with colorectal tumor progression and prognosis: Higher expression in sporadic colorectal tumors compared with ulcerative colitis-associated neoplasia","volume":"216","author":"Sakata","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1097\/IGC.0000000000000123","article-title":"L-type amino acid transporter 1 expression increases in well-differentiated but decreases in poorly differentiated endometrial endometrioid adenocarcinoma and shows an inverse correlation with p53 expression","volume":"24","author":"Watanabe","year":"2014","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00428-020-02781-0","article-title":"Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus","volume":"477","author":"Sato","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, J., Fei, X., Wu, W., Chen, X., Su, L., Zhu, Z., and Zhou, Y. (2016). SLC7A5 functions as a downstream target modulated by CRKL in metastasis process of gastric cancer SGC-7901 Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166147"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1007\/s13277-013-0861-5","article-title":"The impact of L-type amino acid transporter 1 (LAT1) in human hepatocellular carcinoma","volume":"34","author":"Li","year":"2013","journal-title":"Tumor Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/sj.bjc.6604235","article-title":"Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I\u2013III nonsmall cell lung cancer","volume":"98","author":"Kaira","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/j.1365-2559.2009.03300.x","article-title":"L-type amino acid transporter 1 expression is a prognostic marker in patients with surgically resected stage I non-small cell lung cancer","volume":"54","author":"Imai","year":"2009","journal-title":"Histopathology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.lungcan.2009.05.020","article-title":"LAT1 expression in non-small-cell lung carcinomas: Analyses by semiquantitative reverse transcription-PCR (237 cases) and immunohistochemistry (295 cases)","volume":"68","author":"Takeuchi","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_52","first-page":"468","article-title":"LAT1 expression is closely associated with hypoxic markers and mTOR in resected non-small cell lung cancer","volume":"3","author":"Kaira","year":"2011","journal-title":"Am. J. Transl. Res."},{"key":"ref_53","first-page":"3775","article-title":"Relationship between LAT1 expression and response to platinum-based chemotherapy in non-small cell lung cancer patients with postoperative recurrence","volume":"31","author":"Kaira","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/bjc.2012.310","article-title":"Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer","volume":"107","author":"Kaira","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1136\/jclinpath-2012-200826","article-title":"High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas","volume":"65","author":"Yanagisawa","year":"2012","journal-title":"J. Clin. Pathol."},{"key":"ref_56","first-page":"1499","article-title":"An anti-ASCT2 monoclonal antibody suppresses gastric cancer growth by inducing oxidative stress and antibody dependent cellular toxicity in preclinical models","volume":"8","author":"Hosomi","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1349-7006.2011.02151.x","article-title":"Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis","volume":"103","author":"Furuya","year":"2012","journal-title":"Cancer Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/IGC.0b013e3181d28e13","article-title":"Properties of L-type amino acid transporter 1 in epidermal ovarian cancer","volume":"20","author":"Kaji","year":"2010","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16776","DOI":"10.1038\/s41598-019-53397-7","article-title":"Characterization of the expression of LAT1 as a prognostic indicator and a therapeutic target in renal cell carcinoma","volume":"9","author":"Higuchi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.prp.2008.02.003","article-title":"Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung","volume":"204","author":"Kaira","year":"2008","journal-title":"Pathol. Res. Pract."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1245\/s10434-009-0685-0","article-title":"CD98 expression is associated with poor prognosis in resected non-small-cell lung cancer with lymph node metastases","volume":"16","author":"Kaira","year":"2009","journal-title":"Ann. Surg. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1349-7006.2008.01029.x","article-title":"Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in early stage squamous cell carcinoma of the lung","volume":"100","author":"Kaira","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"799","DOI":"10.3892\/etm.2010.117","article-title":"Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in surgically resectable stage III non-small cell lung cancer","volume":"1","author":"Kaira","year":"2010","journal-title":"Exp. Ther. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.nucmedbio.2010.06.004","article-title":"Comparison of L-type amino acid transporter 1 expression and L-[3-18F]-\u03b1-methyl tyrosine uptake in outcome of non-small cell lung cancer","volume":"37","author":"Kaira","year":"2010","journal-title":"Nucl. Med. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1440-1827.2008.02319.x","article-title":"L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer","volume":"59","author":"Sakata","year":"2009","journal-title":"Pathol. Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The Hallmarks of Cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/s42255-019-0039-6","article-title":"Critical role of ASCT2-mediated amino acid metabolism in promoting leukaemia development and progression","volume":"1","author":"Ni","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4080","DOI":"10.4049\/jimmunol.1300923","article-title":"LAT1 is a critical transporter of essential amino acids for immune reactions in activated human T cells","volume":"191","author":"Hayashi","year":"2013","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.immuni.2014.04.007","article-title":"Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation","volume":"40","author":"Nakaya","year":"2014","journal-title":"Immunity"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nri2887","article-title":"Mechanisms for T cell receptor triggering","volume":"11","author":"Dushek","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","first-page":"1373","article-title":"CD98 at the crossroads of adaptive immunity and cancer","volume":"125","author":"Cantor","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Masle-Farquhar, E., Br\u00f6er, A., Yabas, M., Enders, A., and Br\u00f6er, S. (2017). ASCT2 (SLC1A5)-deficient mice have normal B-cell development, proliferation, and antibody production. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00549"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.cellsig.2014.04.002","article-title":"Downregulation of LAT1 expression suppresses cholangiocarcinoma cell invasion and migration","volume":"26","author":"Janpipatkul","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1111\/j.1349-7006.2008.00969.x","article-title":"L-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms","volume":"99","author":"Kaira","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1074\/jbc.RA117.001103","article-title":"GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis","volume":"293","author":"Ding","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_76","first-page":"356","article-title":"Relationship between CD147 and expression of amino acid transporters (LAT1 and ASCT2) in patients with pancreatic cancer","volume":"7","author":"Kaira","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jso.21277","article-title":"L-type amino acid transporter 1 (LAT1) is frequently expressed in thymic carcinomas but is absent in thymomas","volume":"99","author":"Kaira","year":"2009","journal-title":"J. Surg. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Haining, Z., Kawai, N., Miyake, K., Okada, M., Okubo, S., Zhang, X., Fei, Z., and Tamiya, T. (2012). Relation of LAT1\/4F2hc expression with pathological grade, proliferation and angiogenesis in human gliomas. BMC Clin. Pathol., 12.","DOI":"10.1186\/1472-6890-12-4"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.phymed.2018.12.011","article-title":"Topotecan induces apoptosis via ASCT2 mediated oxidative stress in gastric cancer","volume":"57","author":"Wang","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1002\/ijc.29535","article-title":"Targeting SLC1a5-mediated glutamine dependence in non-small cell lung cancer","volume":"137","author":"Hassanein","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"C55","DOI":"10.1152\/ajpcell.00330.2006","article-title":"ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells","volume":"293","author":"Fuchs","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"G467","DOI":"10.1152\/ajpgi.00344.2003","article-title":"Inducible antisense RNA targeting amino acid transporter ATB0\/ASCT2 elicits apoptosis in human hepatoma cells","volume":"286","author":"Fuchs","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nm.4464","article-title":"Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models","volume":"24","author":"Schulte","year":"2018","journal-title":"Nat. Med."},{"key":"ref_84","first-page":"48","article-title":"Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update","volume":"2","author":"Bethune","year":"2010","journal-title":"J. Thorac. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.canlet.2016.07.020","article-title":"ASCT2 (SLC1A5) is an EGFR-associated protein that can be co-targeted by cetuximab to sensitize cancer cells to ROS-induced apoptosis","volume":"381","author":"Lu","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1248\/bpb.31.1096","article-title":"BCH, an inhibitor of system L amino acid transporters, induces apoptosis in cancer cells","volume":"31","author":"Kim","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1227\/01.neu.0000316018.51292.19","article-title":"Enhanced tumor growth elcited by L-type amino acid transporter 1 in human malignant glioma cells","volume":"62","author":"Kobayashi","year":"2008","journal-title":"Neurosurgery"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1007\/s10620-007-0120-y","article-title":"In human entrocytes, GLN transport and ASCT2 surface expression induced by short-term EGF are MAPK, PI3K, and Rho-dependent","volume":"53","author":"Avissar","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/hep.29183","article-title":"A functional mammalian target of rapamycin complex 1 signaling is indispensable for c-Myc-driven hepatocarcinogenesis","volume":"66","author":"Liu","year":"2017","journal-title":"Hepatology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/onc.2012.635","article-title":"Control of glutamine metabolism by the tumor suppressor Rb","volume":"33","author":"Reynolds","year":"2014","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"13194","DOI":"10.1074\/jbc.M115.700534","article-title":"Deletion of amino acid transporter ASCT2 (SLC1A5) reveals an essential role for transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to sustain glutaminolysis in cancer cells","volume":"291","author":"Rahimi","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.mam.2012.07.012","article-title":"Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects","volume":"34","author":"Schioth","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.1158\/0008-5472.CAN-15-3376","article-title":"Genetic disruption of the multifunctional CD98\/LAT1 complex demonstrates the key role of essential amino acid transport in the control of mTORC1 and tumor growth","volume":"76","author":"Cormerais","year":"2016","journal-title":"Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7250","DOI":"10.1038\/ncomms8250","article-title":"LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation","volume":"6","author":"Milkereit","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_95","first-page":"4819","article-title":"Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer","volume":"30","author":"Imai","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_96","first-page":"885","article-title":"Inhibition of system L (LAT1\/CD98hc) reduces the growth of cultured human breast cancer cells","volume":"20","author":"Shennan","year":"2008","journal-title":"Oncol. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/jso.1165","article-title":"Expression of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in liver tumor lesions of rat models","volume":"78","author":"Ohkame","year":"2001","journal-title":"J. Surg. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1248\/bpb.33.1117","article-title":"Inhibition of L-type amino acid transporter modulates the expression of cell cycle regulatory factors in KB oralcancer cells","volume":"33","author":"Kim","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3109\/10799893.2010.488649","article-title":"Selective inhibition of proteins regulating CDK\/cyclin complexes: Strategy against cancer\u2014A review","volume":"30","author":"Ramasree","year":"2010","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"18782","DOI":"10.1073\/pnas.0810199105","article-title":"Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction","volume":"105","author":"Wise","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ccell.2015.02.006","article-title":"Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies","volume":"27","author":"Jeon","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.bbamcr.2015.02.020","article-title":"IL4 receptor \u03b1 mediates enhanced glucose and glutamine metabolism to support breast cancer growth","volume":"1853","author":"Venmar","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1101\/gad.1985910","article-title":"The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism","volume":"24","author":"Wellen","year":"2010","journal-title":"Genes Dev."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/path.4429","article-title":"ATF4 and N-Myc coordinate glutamine metabolism in MYCN-amplified neuroblastoma cells through ASCT2 activation","volume":"235","author":"Ren","year":"2015","journal-title":"J. Pathol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e356","DOI":"10.1038\/oncsis.2017.59","article-title":"Epigenetic silencing of microRNA-137 enhances ASCT2 expression and tumor glutamine metabolism","volume":"6","author":"Dong","year":"2017","journal-title":"Oncogenesis"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/s41418-017-0053-8","article-title":"miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma","volume":"25","author":"Luo","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Rajasinghe, L.D., Hutchings, M., and Gupta, S.V. (2019). Delta-tocotrienol modulates glutamine dependence by inhibiting ASCT2 and LAT1 transporters in non-small cell lung cancer (NSCLC) cells: A metabolomic approach. Metabolites, 9.","DOI":"10.3390\/metabo9030050"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sevigny, C.M., Sengupta, S., Luo, Z., Liu, X., Hu, R., Zhang, Z., Jin, L., Pearce, D., Demas, D., and Shajahan-Haq, A.N. (2019). SLCs contribute to endocrine resistance in breast cancer: Role of SLC7A5 (LAT1). BioRxiv.","DOI":"10.1101\/555342"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Sharma, A., Boise, L.H., and Shanmugam, M. (2019). Cancer metabolism and the evasion of apoptotic cell death. Cancers, 11.","DOI":"10.3390\/cancers11081144"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/cdd.2014.216","article-title":"Old, new and emerging functions of caspases","volume":"22","author":"Shalini","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_111","first-page":"1281","article-title":"L-type amino acid transport and cancer: Targeting the mTORC1 pathway to inhibit neoplasia","volume":"5","author":"Wang","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1083\/jcb.201306041","article-title":"Where is mTOR and what is it doing there?","volume":"203","author":"Betz","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1038\/onc.2015.381","article-title":"ASCT2\/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer","volume":"35","author":"Wang","year":"2016","journal-title":"Oncogene"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/ijc.28749","article-title":"Targeting glutamine transport to suppress melanoma cell growth","volume":"135","author":"Wang","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1182\/blood-2013-03-493163","article-title":"Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia","volume":"122","author":"Willems","year":"2013","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00432-018-2605-9","article-title":"Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth","volume":"144","author":"Ye","year":"2018","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.bcp.2010.05.021","article-title":"Impact of system L amino acid transporter 1 (LAT1) on proliferation of human ovarian cancer cells: A possible target for combination therapy with anti-proliferative aminopeptidase inhibitors","volume":"80","author":"Fan","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cell.2008.11.044","article-title":"Bidirectional transport of amino acids regulates mTOR and autophagy","volume":"136","author":"Nicklin","year":"2009","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1074\/jbc.RA117.001342","article-title":"The glutamine transporter ASCT2 (SLC1A5) promotes tumor growth independently of the amino acid transporter LAT1 (SLC7A5)","volume":"293","author":"Cormerais","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Bothwell, P.J., Kron, C.D., Wittke, E.F., Czerniak, B.N., and Bode, B.P. (2018). Targeted suppression and knockout of ASCT2 or LAT1 in epithelial and mesenchymal human liver cancer cells fail to inhibit growth. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072093"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3892\/ol.2013.1342","article-title":"Downregulation of L-type amino acid transporter 1 expression inhibits the growth, migration and invasion of gastric cancer cells","volume":"6","author":"Shi","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.prp.2015.03.007","article-title":"L-Type amino acid transporter 1 (LAT1) expression in lymph node metastasis of gastric carcinoma: Its correlation with size of metastatic lesion and Ki-67 labeling","volume":"211","author":"Ichinoe","year":"2015","journal-title":"Pathol. Res. Pract."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.trecan.2017.01.005","article-title":"Glutamine Metabolism in Cancer: Understanding the Heterogeneity","volume":"3","author":"Cluntun","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tibs.2010.05.003","article-title":"Glutamine addiction: A new therapeutic target in cancer","volume":"35","author":"Wise","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Scalise, M., Pochini, L., Galluccio, M., Console, L., and Indiveri, C. (2017). Glutamine transport and mitochondrial metabolism in cancer cell growth. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00306"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-bioeng-071516-044546","article-title":"Glutaminolysis: A hallmark of cancer metabolism","volume":"19","author":"Yang","year":"2017","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/bcr554","article-title":"Host microenvironment in breast cancer development: Inflammatory cells, cytokines and chemokines in breast cancer progression: Reciprocal tumor\u2013microenvironment interactions","volume":"5","year":"2002","journal-title":"Breast Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.jaci.2010.11.050","article-title":"Interleukins, from 1 to 37, and interferon-\u03b3: Receptors, functions, and roles in diseases","volume":"127","author":"Akdis","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00726-015-2067-1","article-title":"The role of leucine and its metabolites in protein and energy metabolism","volume":"48","author":"Duan","year":"2016","journal-title":"Amino Acids"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/14728222.2019.1627328","article-title":"ASCT2: A potential cancer drug target","volume":"23","author":"Wahi","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1158\/0008-5472.CAN-14-3745","article-title":"Amino acid transporters in cancer and their relevance to \u201cglutamine addiction\u201d: Novel targets for the design of a new class of anticancer drugs","volume":"75","author":"Bhutia","year":"2015","journal-title":"Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1517\/14728222.2015.1044975","article-title":"Targeting L-type amino acid transporter 1 for anticancer therapy: Clinical impact from diagnostics to therapeutics","volume":"19","author":"Jin","year":"2015","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Zhang, C., Xu, J., Xue, S., and Ye, J. (2020). Prognostic value of L-type amino acid transporter 1 (LAT1) in various cancers: A meta-analysis. Mol. Diagn. Ther.","DOI":"10.1007\/s40291-020-00470-x"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Lu, J.J., Li, P., Yang, Y., Wang, L., Zhang, Y., Zhu, J.Y., Zhu, X.R., and Chen, M.B. (2020). Prognostic value of LAT-1 status in solid cancer: A systematic review and meta-analysis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0233629"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.humpath.2018.09.020","article-title":"Expression of amino acid transporter (LAT1 and 4F2hc) in pulmonary pleomorphic carcinoma","volume":"84","author":"Kaira","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.lungcan.2008.12.015","article-title":"Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in stage I pulmonary adenocarcinoma","volume":"66","author":"Kaira","year":"2009","journal-title":"Lung Cancer"},{"key":"ref_137","first-page":"4223","article-title":"L-type amino-acid transporter 1 expression predicts the response to preoperative hyperthermo-chemoradiotherapy for advanced rectal cancer","volume":"30","author":"Ebara","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.21873\/anticanres.13375","article-title":"Role of amino acid transporter expression as a prognostic marker in patients with surgically resected colorectal cancer","volume":"39","author":"Ogawa","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s00428-019-02520-0","article-title":"Significant relationship between the LAT1 expression pattern and chemoresistance in ovarian clear cell carcinoma","volume":"474","author":"Sato","year":"2019","journal-title":"Virchows Arch."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1038\/bjc.2014.178","article-title":"Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer","volume":"110","author":"Toyoda","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1111\/cas.12529","article-title":"Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma","volume":"105","author":"Isoda","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/CMR.0000000000000181","article-title":"Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma","volume":"25","author":"Shimizu","year":"2015","journal-title":"Melanoma Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.parint.2015.11.011","article-title":"Increase in L-type amino acid transporter 1 expression during cholangiocarcinogenesis caused by liver fluke infection and its prognostic significance","volume":"66","author":"Yothaisong","year":"2017","journal-title":"Parasitol. Int."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Kaira, K., Sunose, Y., Ohshima, Y., Ishioka, N.S., Arakawa, K., Ogawa, T., Sunaga, N., Shimizu, K., Tominaga, H., and Oriuchi, N. (2013). Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-482"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/cam4.272","article-title":"High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas","volume":"3","author":"Yanagisawa","year":"2014","journal-title":"Cancer Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s12253-015-9954-3","article-title":"Expression of amino acid transporters (LAT1 and ASCT2) in patients with stage III\/IV laryngeal squamous cell carcinoma","volume":"21","author":"Nikkuni","year":"2015","journal-title":"Pathol. Oncol. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/s41598-020-58136-x","article-title":"Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma","volume":"10","author":"Maimaiti","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3233\/CBM-150486","article-title":"L-amino acid transporter 1 may be a prognostic marker for local progression of prostatic cancer under expectant management","volume":"15","author":"Yanagisawa","year":"2015","journal-title":"Cancer Biomark."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00280-017-3477-4","article-title":"Relationship between LAT1 expression and resistance to chemotherapy in pancreatic ductal adenocarcinoma","volume":"81","author":"Altan","year":"2018","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1620\/tjem.246.167","article-title":"L-Type Amino Acid Transporter 1 Immunoreactivity as a Possible Diagnostic and Prognostic Marker of Thymic Carcinoma","volume":"246","author":"Maeda","year":"2018","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Toda, K., Nishikawa, G., Iwamoto, M., Itatani, Y., Takahashi, R., Sakai, Y., and Kawada, K. (2017). Clinical role of ASCT2 (SLC1A5) in KRAS-mutated colorectal cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081632"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Bjersand, K., Seidal, T., Sundstr\u00f6m-Poromaa, I., \u00c5kerud, H., and Skirnisdottir, I. (2017). The clinical and prognostic correlation of HRNPM and SLC1A5 in pathogenesis and prognosis in epithelial ovarian cancer. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179363"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13058-017-0905-7","article-title":"Proteomic profiling of breast cancer metabolism identifies SHMT2 and ASCT2 as prognostic factors","volume":"19","author":"Bernhardt","year":"2017","journal-title":"Breast Cancer Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.7314\/APJCP.2015.16.9.4103","article-title":"Genetic Variants in ASCT2 Gene are Associated with the Prognosis of Transarterial Chemoembolisation-Treated Early- Stage Hepatocelluar Carcinoma","volume":"16","author":"Ge","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_155","first-page":"1126","article-title":"Clinical significance of coexpression of L-type amino acid transporter 1 (LAT1) and ASC amino acid transporter 2 (ASCT2) in lung adenocarcinoma","volume":"7","author":"Yazawa","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/jso.24160","article-title":"Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma","volume":"113","author":"Honjo","year":"2016","journal-title":"J. Surg. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Hafliger, P., and Charles, R.P. (2019). The L-type amino acid transporter LAT1-An Emerging Target in Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102428"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4251\/wjgo.v9.i1.21","article-title":"Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment","volume":"9","author":"Hayashi","year":"2017","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"104844","DOI":"10.1016\/j.phrs.2020.104844","article-title":"Target the human Alanine\/Serine\/Cysteine Transporter 2(ASCT2): Achievement and future for novel cancer therapy","volume":"158","author":"Jiang","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1113\/jphysiol.2004.062521","article-title":"New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak","volume":"557","author":"Grewer","year":"2004","journal-title":"J. Physiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.bmc.2004.11.028","article-title":"N\u03b3-Aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site","volume":"13","author":"Esslinger","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1085\/jgp.201812276","article-title":"Novel alanine serine cysteine transporter 2 (ASCT2) inhibitors based on sulfonamide and sulfonic acid ester scaffolds","volume":"151","author":"Ndaru","year":"2019","journal-title":"J. Gen. Physiol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuropharm.2017.08.010","article-title":"Phenylglycine analogs are inhibitors of the neutral amino acid transporters ASCT1 and ASCT2 and enhance NMDA receptor-mediated LTP in rat visual cortex slices","volume":"126","author":"Foster","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Colas, C., Grewer, C., Otte, N.J., Gameiro, A., Albers, T., Singh, K., Shere, H., Bonomi, M., Holst, J., and Schlessinger, A. (2015). Ligand discovery for the Alanine-Serine-Cysteine Transporter (ASCT2, SLC1A5) from homology modeling and virtual screening. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004477"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bmcl.2016.12.063","article-title":"Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2","volume":"27","author":"Singh","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.bbrc.2016.11.089","article-title":"Establishment of monoclonal antibodies against cell surface domains of ASCT2\/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth","volume":"482","author":"Suzuki","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_167","first-page":"3399","article-title":"Anti-tumor efficacy evaluation of a novel monoclonal antibody targeting neutral amino acid transporter ASCT2 using patient-derived xenograft mouse models of gastric cancer","volume":"9","author":"Kasai","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s00726-017-2436-z","article-title":"GPNA inhibits the sodium-independent transport system l for neutral amino acids","volume":"49","author":"Chiu","year":"2017","journal-title":"Amino Acids"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1111\/cas.13021","article-title":"Efficacy of system L amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma","volume":"107","author":"Ohshima","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"599","DOI":"10.4196\/kjpp.2017.21.6.599","article-title":"JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells","volume":"21","author":"Choi","year":"2017","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1038\/leu.2014.338","article-title":"L-type amino-acid transporter 1 (LAT1): A therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma\/T-cell acute lymphoblastic leukemia","volume":"29","author":"Rosilio","year":"2015","journal-title":"Leukemia"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1254\/jphs.13154FP","article-title":"JPH203, an L-type amino acid transporter 1\u2013selective compound, induces apoptosis of YD-38 human oral cancer cells","volume":"124","author":"Yun","year":"2014","journal-title":"J. Pharmacol. Sci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"159","DOI":"10.21873\/anticanres.13092","article-title":"Different response profiles of gastrointestinal cancer cells to an L-type amino acid transporter inhibitor, JPH203","volume":"39","author":"Muto","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jphs.2020.06.006","article-title":"JPH203, a newly developed anti-cancer drug, shows a preincubation inhibitory effect on L-type amino acid transporter 1 function","volume":"144","author":"Okunushi","year":"2020","journal-title":"J. Pharmacol. Sci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1073\/pnas.1218165110","article-title":"Structure-based ligand discovery for the Large-neutral Amino Acid Transporter 1, LAT-1","volume":"110","author":"Geier","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jphs.2017.01.006","article-title":"Structure-activity relationship of a novel series of inhibitors for cancer type transporter L-type amino acid transporter 1 (LAT1)","volume":"133","author":"Kongpracha","year":"2017","journal-title":"J. Pharmacol. Sci."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.bcp.2017.07.006","article-title":"Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs","volume":"143","author":"Napolitano","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Okano, N., Naruge, D., Kawai, K., Kobayashi, T., Nagashima, F., Endou, H., and Furuse, J. (2020). First-in-human phase I study of JPH203, an L-type amino acid transporter 1 inhibitor, in patients with advanced solid tumors. Investig. New Drugs.","DOI":"10.1007\/s10637-020-00924-3"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/BF02980218","article-title":"Gene expression profiles in t24 human bladder carcinoma cells by inhibiting an l-type amino acid transporter, lat1","volume":"30","author":"Baniasadi","year":"2007","journal-title":"Arch. Pharm. Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s13139-010-0068-2","article-title":"Potential biomarker of L-type amino acid transporter 1 in breast cancer progression","volume":"45","author":"Liang","year":"2011","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1002\/ijc.30371","article-title":"LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma","volume":"139","author":"Marshall","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.canlet.2008.10.035","article-title":"System L amino acid transporter inhibitor enhances anti-tumor activity of cisplatin in a head and neck squamous cell carcinoma cell line","volume":"276","author":"Yamauchi","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bbrc.2013.08.020","article-title":"A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model","volume":"439","author":"Fukumoto","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/pros.23263","article-title":"Prostate cancer cells in different androgen receptor status employ different leucine transporters","volume":"77","author":"Otsuki","year":"2017","journal-title":"Prostate"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"7525","DOI":"10.1158\/0008-5472.CAN-11-1821","article-title":"Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression","volume":"71","author":"Wang","year":"2011","journal-title":"Cancer Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.jconrel.2014.06.038","article-title":"Insight into nanoparticle cellular uptake and intracellular targeting","volume":"190","author":"Yameen","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Kou, L., Bhutia, Y.D., Yao, Q., He, Z., Sun, J., and Ganapathy, V. (2018). Transporter-guided delivery of nanoparticles to improve drug permeation across cellular barriers and drug exposure to selective cell types. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00027"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1007\/s11051-013-2022-6","article-title":"Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting","volume":"15","author":"Kharya","year":"2013","journal-title":"J. Nanopart. Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.nano.2016.11.012","article-title":"Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy","volume":"13","author":"Li","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"39259","DOI":"10.1021\/acsami.7b14851","article-title":"Multibranched gold nanoparticles with intrinsic LAT-1 targeting capabilities for selective photothermal therapy of breast cancer","volume":"9","author":"Ong","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"6443","DOI":"10.1021\/acsomega.9b00216","article-title":"LAT1-targeting thermoresponsive liposomes for effective cellular uptake by cancer cells","volume":"4","author":"Fujieda","year":"2019","journal-title":"ACS Omega"},{"key":"ref_192","first-page":"321","article-title":"(18)F-FBPA as a tumor specific tracer of L-type amino acid transporter 1 (LAT1): PET evaluation in tumor and inflammation compared to (18)F-FDG and (11)C-methionine","volume":"18","author":"Watabe","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"15718","DOI":"10.1038\/s41598-019-52270-x","article-title":"(18)F-FIMP: A LAT1-specific PET probe for discrimination between tumor tissue and inflammation","volume":"9","author":"Nozaki","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.nucmedbio.2019.12.002","article-title":"2-[(18)F]FELP, a novel LAT1-specific PET tracer, for the discrimination between glioblastoma, radiation necrosis and inflammation","volume":"82","author":"Verhoeven","year":"2020","journal-title":"Nucl. Med. Biol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/2\/203\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:08:24Z","timestamp":1760159304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/2\/203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":194,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["cancers13020203"],"URL":"https:\/\/doi.org\/10.3390\/cancers13020203","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]}}}