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Prognostic Value of L-Type Amino Acid Transporter 1 (LAT1) in Various Cancers: A Meta-Analysis

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Abstract

Background and Objective

The L-type amino acid transporter 1 (LAT1, SLC7A5) is overexpressed in various types of cancer and has been thought to assist cancer progression through its uptake of neutral amino acids. However, the prognostic role of LAT1 in human cancers remains uncharacterized. Therefore, we conducted this meta-analysis to determine the prognostic significance of LAT1 in various cancers.

Methods

We systematically searched the PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and WanFang databases to collect relevant cohort studies investigating the prognostic value of LAT1 expression in patients with cancer. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to clarify the association between the LAT1 expression and the survival of patients with cancer. Odds ratios (ORs) with 95% CIs were calculated to appraise the correlation between LAT1 and the clinicopathological characteristics in patients with cancer.

Results

A total of 32 eligible articles, including 34 cohorts and 6410 patients, were enrolled in this meta-analysis. Our results demonstrated that high LAT1 expression was significantly associated with poor overall survival (HR = 1.66, 95% CI 1.41–1.96, P < 0.001), cancer-specific survival (HR = 1.64, 95% CI 1.31–2.05, P < 0.001), disease-free survival (HR = 1.55, 95% CI 1.31–1.83, P < 0.001), and progression-free survival (HR = 1.18, 95% CI 1.02–1.37, P = 0.026) in patients with cancer. In addition, we found that the elevated expression level of LAT1 was significantly related to certain phenotypes of tumor aggressiveness, such as tumor size, clinical stage, T stage, lymphatic invasion, vascular invasion, tumor differentiation, Ki-67, CD34, CD98, p53, and system ASC amino acid transporter-2.

Conclusions

Elevated expression of LAT1 is associated with poor prognosis in human cancers and may serve as a potential prognostic marker and therapeutic target for patients with malignancies.

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References

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    PubMed  CAS  Google Scholar 

  2. Danhier P, Bański P, Payen VL, Grasso D, Ippolito L, Sonveaux P, Porporato PE. Cancer metabolism in space and time: beyond the Warburg effect. Biochim Biophys Acta BBA Bioenerget. 2017;1858(8):556–72.

    CAS  Google Scholar 

  3. Bond P. Regulation of mTORC1 by growth factors, energy status, amino acids and mechanical stimuli at a glance. J Int Soci Sports Nutr. 2016;13(1):8.

    Google Scholar 

  4. Bar-Peled L, Sabatini DM. Regulation of mTORC1 by amino acids. Trends Cell Biol. 2014;24(7):400–6.

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Fuchs BC, Bode BP. Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol. 2005;15(4):254–66.

    PubMed  CAS  Google Scholar 

  6. Patel M, Dalvi P, Gokulgandhi M, Kesh S, Kohli T, Pal D, Mitra AK. Functional characterization and molecular expression of large neutral amino acid transporter (LAT1) in human prostate cancer cells. Int J Pharm. 2013;443(1–2):245–53.

    PubMed  CAS  Google Scholar 

  7. Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, Cha SH, Matsuo H, Fukushima J, Fukasawa Y, Tani Y, Taketani Y, Uchino H, Kim JY, Inatomi J, Okayasu I, Miyamoto K, Takeda E, Goya T, Endou H. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta BBA Biomembr. 2001;1514(2):291–302.

    CAS  Google Scholar 

  8. Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H. Expression Cloning and Characterization of a Transporter for Large Neutral Amino Acids Activated by the Heavy Chain of 4F2 Antigen (CD98). J Biol Chem. 1998;273(37):23629–32.

    PubMed  CAS  Google Scholar 

  9. Xu M, Sakamoto S, Matsushima J, Kimura T, Ueda T, Mizokami A, Kanai Y, Ichikawa T. Up-regulation of LAT1 during antiandrogen therapy contributes to progression in prostate cancer cell. J Urol. 2016;195(5):1588–97.

    PubMed  Google Scholar 

  10. Yazawa T, Shimizu K, Kaira K, Nagashima T, Ohtaki Y, Atsumi J, Obayashi K, Nagamori S, Kanai Y, Oyama T, Takeyoshi I. Clinical significance of coexpression of L-type amino acid transporter 1 (LAT1) and ASC amino acid transporter 2 (ASCT2) in lung adenocarcinoma. Am J Transl Res. 2015;7(6):1126–39.

    PubMed  PubMed Central  CAS  Google Scholar 

  11. Kaira K, Kawashima O, Endoh H, Imaizumi K, Goto Y, Kamiyoshihara M, Sugano M, Yamamoto R, Osaki T, Tanaka S, Fujita A, Imai H, Kogure Y, Seki Y, Shimizu K, Mogi A, Shitara Y, Oyama T, Kanai Y, Asao T. Expression of amino acid transporter (LAT1 and 4F2hc) in pulmonary pleomorphic carcinoma. Hum Pathol. 2019;84:142–9.

    PubMed  CAS  Google Scholar 

  12. Koshi H, Sano T, Handa T, Yanagawa T, Saitou K, Nagamori S, Kanai Y, Takagishi K, Oyama T. L-type amino acid transporter-1 and CD98 expression in bone and soft tissue tumors. Pathol Int. 2015;65(9):460–7.

    PubMed  CAS  Google Scholar 

  13. Marshall AD, van Geldermalsen M, Otte NJ, Anderson LA, Lum T, Vellozzi MA, Zhang BK, Thoeng A, Wang Q, Rasko JEJ, Holst J. LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma. Int J Cancer. 2016;139(11):2529–39.

    PubMed  CAS  Google Scholar 

  14. Ichinoe M, Yanagisawa N, Mikami T, Hana K, Nakada N, Endou H, Okayasu I, Murakumo Y. 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. Pathol Res. 2015;211(7):533–8.

    CAS  Google Scholar 

  15. Bolzoni M, Chiu M, Accardi F, Vescovini R, Airoldi I, Storti P, Todoerti K, Agnelli L, Missale G, Andreoli R, Bianchi MG, Allegri M, Barilli A, Nicolini F, Cavalli A, Costa F, Marchica V, Toscani D, Mancini C, Martella E, Dall Asta V, Donofrio G, Aversa F, Bussolati O, Giuliani N. Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target. Blood. 2016;128(5):667–79.

    PubMed  CAS  Google Scholar 

  16. Hashimoto H, Kurata A, Kikuchi H, Masuda Y, Fujita K, Okuyama R, Inoue S, Horiuchi H, Kuroda M. L-type amino acid transporter 1 expression in esophageal carcinogenesis according to WHO and Japanese classifications of intraepithelial neoplasia. Pathol Int. 2017;67(5):247–55.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  18. Ohshima Y, Kaira K, Yamaguchi A, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Yokobori T, Miyazaki T, Asao T, Tsushima Y, Kuwano H, Ishioka NS. Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma. Cancer Sci. 2016;107(10):1499–505.

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Rosilio C, Nebout M, Imbert V, Griessinger E, Neffati Z, Benadiba J, Hagenbeek T, Spits H, Reverso J, Ambrosetti D, Michiels JF, Bailly-Maitre B, Endou H, Wempe MF, Peyron JF. 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.

    PubMed  CAS  Google Scholar 

  20. Häfliger P, Graff J, Rubin M, Stooss A, Dettmer MS, Altmann K, Gertsch J, Charles R. The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model. J Exp Clin Cancer Res. 2018;37(1):234.

    PubMed  PubMed Central  Google Scholar 

  21. Cormerais Y, Pagnuzzi Boncompagni M, Schrötter S, Giuliano S, Tambutté E, Endou H, Wempe MF, Pagès G, Pouysségur J, Picco V. Inhibition of the amino-acid transporter LAT1 demonstrates anti-neoplastic activity in medulloblastoma. J Cell Mol Med. 2019;23(4):2711–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Otsuki H, Kimura T, Yamaga T, Kosaka T, Suehiro J, Sakurai H. Prostate cancer cells in different androgen receptor status employ different leucine transporters. Prostate. 2017;77(2):222–33.

    PubMed  CAS  Google Scholar 

  23. Muto Y, Furihata T, Kaneko M, Higuchi K, Okunushi K, Morio H, Reien Y, Uesato M, Matsubara H, Anzai N. Different Response Profiles of Gastrointestinal Cancer Cells to an L-Type Amino Acid Transporter Inhibitor (JPH203. Anticancer Res. 2019;39(1):159–65.

    PubMed  CAS  Google Scholar 

  24. Ogawa H, Kaira K, Motegi Y, Yokobori T, Takada T, Katoh R, Osone K, Takahashi R, Katayama C, Oyama T, Kanai Y, Yao T, Asao T, Kuwano H, Shirabe K. Role of amino acid transporter expression as a prognostic marker in patients with surgically resected colorectal cancer. Anticancer Res. 2019;39(5):2535–43.

    PubMed  CAS  Google Scholar 

  25. Sato K, Miyamoto M, Takano M, Furuya K, Tsuda H. Significant relationship between the LAT1 expression pattern and chemoresistance in ovarian clear cell carcinoma. Virchows Arch. 2019;474(6):701–10.

    PubMed  CAS  Google Scholar 

  26. Higuchi K, Sakamoto S, Ando K, Maimaiti M, Takeshita N, Okunushi K, Reien Y, Imamura Y, Sazuka T, Nakamura K, Matsushima J, Furihata T, Ikehara Y, Ichikawa T, Anzai N. Characterization of the expression of LAT1 as a prognostic indicator and a therapeutic target in renal cell carcinoma. Sci Rep. 2019;9(1):16776.

    PubMed  PubMed Central  Google Scholar 

  27. El Ansari R, Craze ML, Miligy I, Diez-Rodriguez M, Nolan CC, Ellis IO, Rakha EA, Green AR. The amino acid transporter SLC7A5 confers a poor prognosis in the highly proliferative breast cancer subtypes and is a key therapeutic target in luminal B tumours. Breast Cancer Res. 2018;20(1):21.

    PubMed  PubMed Central  Google Scholar 

  28. Altan B, Kaira K, Watanabe A, Kubo N, Bao P, Dolgormaa G, Bilguun EO, Araki K, Kanai Y, Yokobori T, Oyama T, Nishiyama M, Kuwano H, Shirabe K. Relationship between LAT1 expression and resistance to chemotherapy in pancreatic ductal adenocarcinoma. Cancer Chemother Pharmacol. 2018;81(1):141–53.

    PubMed  CAS  Google Scholar 

  29. Shimizu A, Kaira K, Okubo Y, Utsumi D, Yasuda M, Tominaga H, Oriuchi N, Kanai Y, Takahashi K, Ishikawa O. Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma. Neoplasma. 2017;64(02):283–8.

    PubMed  CAS  Google Scholar 

  30. Yothaisong S, Namwat N, Yongvanit P, Khuntikeo N, Puapairoj A, Jutabha P, Anzai N, Tassaneeyakul W, Tangsucharit P, Loilome W. Increase in L-type amino acid transporter 1 expression during cholangiocarcinogenesis caused by liver fluke infection and its prognostic significance. Parasitol Int. 2017;66(4):471–8.

    PubMed  CAS  Google Scholar 

  31. Hayase S, Kumamoto K, Saito K, Kofunato Y, Sato Y, Okayama H, Miyamoto K, Ohki S, Takenoshita S. L-type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncol Lett. 2017;14(6):7410–6.

    PubMed  PubMed Central  Google Scholar 

  32. Honjo H, Kaira K, Miyazaki T, Yokobori T, Kanai Y, Nagamori S, Oyama T, Asao T, Kuwano H. Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma. J Surg Oncol. 2016;113(4):381–9.

    PubMed  CAS  Google Scholar 

  33. Shimizu A, Kaira K, Kato M, Yasuda M, Takahashi A, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Asao T, Ishikawa O. Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma. Melanoma Res. 2015;25(5):399–405.

    PubMed  CAS  Google Scholar 

  34. Namikawa M, Kakizaki S, Kaira K, Tojima H, Yamazaki Y, Horiguchi N, Sato K, Oriuchi N, Tominaga H, Sunose Y, Nagamori S, Kanai Y, Oyama T, Takeyoshi I, Yamada M. Expression of amino acid transporters (LAT1 (ASCT2 and xCT) as clinical significance in hepatocellular carcinoma. Hepatol Res. 2015;45(9):1014–22.

    PubMed  CAS  Google Scholar 

  35. Toyoda M, Kaira K, Shino M, Sakakura K, Takahashi K, Takayasu Y, Tominaga H, Oriuchi N, Nikkuni O, Suzuki M, Iijima M, Tsukamoto N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K. CD98 as a novel prognostic indicator for patients with stage III/IV hypopharyngeal squamous cell carcinoma. Head Neck. 2015;37(11):1569–74.

    PubMed  Google Scholar 

  36. Nikkuni O, Kaira K, Toyoda M, Shino M, Sakakura K, Takahashi K, Tominaga H, Oriuchi N, Suzuki M, Iijima M, Asao T, Nishiyama M, Nagamori S, Kanai Y, Oyama T, Chikamatsu K. 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.

    PubMed  CAS  Google Scholar 

  37. Kaira K, Nakamura K, Hirakawa T, Imai H, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Tsukamoto N, Oyama T, Asao T, Minegishi T. Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in patients with ovarian tumors. Am J Transl Res. 2015;7(6):1161–71.

    PubMed  PubMed Central  CAS  Google Scholar 

  38. Yanagisawa N, Hana K, Nakada N, Ichinoe M, Koizumi W, Endou H, Okayasu I, Murakumo Y. High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas. Cancer Med. 2014;3(5):1246–55.

    PubMed  PubMed Central  CAS  Google Scholar 

  39. Isoda A, Kaira K, Iwashina M, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Oyama T, Asao T, Matsumoto M, Sawamura M. Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma. Cancer Sci. 2014;105(11):1496–502.

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Toyoda M, Kaira K, Ohshima Y, Ishioka NS, Shino M, Sakakura K, Takayasu Y, Takahashi K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K. Prognostic significance of amino-acid transporter expression (LAT1 (ASCT2 (and xCT) in surgically resected tongue cancer. Br J Cancer. 2014;110(10):2506–13.

    PubMed  PubMed Central  CAS  Google Scholar 

  41. Kaira K, Sunose Y, Ohshima Y, Ishioka N, Arakawa K, Ogawa T, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, Itoh H, Nagamori S, Kanai Y, Yamaguchi A, Segawa A, Ide M, Mori M, Oyama T, Takeyoshi I. 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. 2013;13:482.

    PubMed  PubMed Central  Google Scholar 

  42. Li JB, Chen YB, Huang QC, Zhai FL, Bao GQ, He XL, Xing JL. Expression of LAT1 in colorectal cancer and its correlation with the prognosis. Progress Mod Biomed. 2013;13(11):2010–4.

    CAS  Google Scholar 

  43. Li J, Qiang J, Chen S, Wang X, Fu J, Chen Y. The impact of L-type amino acid transporter 1 (LAT1) in human hepatocellular carcinoma. Tumor Biol. 2013;34(5):2977–81.

    CAS  Google Scholar 

  44. Furuya M, Horiguchi J, Nakajima H, Kanai Y, Oyama T. Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis. Cancer Sci. 2012;103(2):382–9.

    PubMed  CAS  Google Scholar 

  45. Yu B, Ding F, Ma H, Zhang R, He Y, Zhang X, Zhou X. Expression of LAT1 in stage I lung adenocarcinoma and its clinical significance. J Clin Exp Pathol. 2012;28(8):838–41.

    Google Scholar 

  46. Kaira K, Sunose Y, Arakawa K, Ogawa T, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, Itoh H, Nagamori S, Kanai Y, Segawa A, Furuya M, Mori M, Oyama T, Takeyoshi I. Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer. Br J Cancer. 2012;107(4):632–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  47. Yanagisawa N, Ichinoe M, Mikami T, Nakada N, Hana K, Koizumi W, Endou H, Okayasu I. High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas. J Clin Pathol. 2012;65(11):1019–23.

    PubMed  Google Scholar 

  48. Ichinoe M, Mikami T, Yoshida T, Igawa I, Tsuruta T, Nakada N, Anzai N, Suzuki Y, Endou H, Okayasu I. High expression of L-type amino-acid transporter 1 (LAT1) in gastric carcinomas: comparison with non-cancerous lesions. Pathol Int. 2011;61(5):281–9.

    PubMed  CAS  Google Scholar 

  49. Kaira K, Nakagawa K, Ohde Y, Okumura T, Takahashi T, Murakami H, Endo M, Kondo H, Nakajima T, Yamamoto N. Depolarized MUC1 expression is closely associated with hypoxic markers and poor outcome in resected non–small cell lung cancer. Int J Surg Pathol. 2012;20(3):223–32.

    PubMed  Google Scholar 

  50. Kaira K, Oriuchi N, Shimizu K, Imai H, Tominaga H, Yanagitani N, Sunaga N, Hisada T, Ishizuka T, Kanai Y, Oyama T, Mori M, Endo K. Comparison of l-type amino acid transporter 1 expression and l-[3-18F]-α-methyl tyrosine uptake in outcome of non-small cell lung cancer. Nucl Med Biol. 2010;37(8):911–6.

    PubMed  CAS  Google Scholar 

  51. Takeuchi K, Ogata S, Nakanishi K, Ozeki Y, Hiroi S, Tominaga S, Aida S, Matsuo H, Sakata T, Kawai T. LAT1 expression in non-small-cell lung carcinomas: analyses by semiquantitative reverse transcription-PCR (237 cases) and immunohistochemistry (295 cases). Lung Cancer. 2010;68(1):58–65.

    PubMed  Google Scholar 

  52. Sakata T, Ferdous G, Tsuruta T, Satoh T, Okayasu I. L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int. 2009;59(1):7–18.

    PubMed  CAS  Google Scholar 

  53. Kaira K, Oriuchi N, Imai H, Shimizu K, Yanagitani N. Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer. Br J Cancer. 2008;98(4):742–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  54. Nakanishi K, Ogata S, Matsuo H, Kanai Y, Endou H. Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract. Virchows Arch. 2007;451(3):681–90.

    PubMed  CAS  Google Scholar 

  55. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.

    PubMed  Google Scholar 

  56. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med. 2007;26(25):4544–62.

    PubMed  Google Scholar 

  57. Ichinoe M, Yanagisawa N, Mikami T, Hana K, Nakada N, Endou H, Okayasu I, Murakumo Y. 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. Pathol Res Pract. 2015;211(7):533–8.

    PubMed  CAS  Google Scholar 

  58. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. 2006;124(3):471–84.

    CAS  Google Scholar 

  59. Wise DR, Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci. 2010;35(8):427–33.

    PubMed  PubMed Central  CAS  Google Scholar 

  60. Klionsky DJ. Autophagy revisited: a conversation with christian de duve. Autophagy. 2008;4(6):740–3.

    PubMed  Google Scholar 

  61. Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1 (an autophagy gene essential for early embryonic development (is a haploin sufficient tumor suppressor. Proc Natl Acad Sci USA. 2003;100(25):15077–82.

    PubMed  CAS  PubMed Central  Google Scholar 

  62. White E. The role for autophagy in cancer. J Clin Investig. 2015;125(1):42–6.

    PubMed  PubMed Central  Google Scholar 

  63. Salisbury T, Arthur S. The regulation and function of the L-type amino acid transporter 1 (LAT1) in cancer. Int J Mol Sci. 2018;19(8):2373.

    PubMed Central  Google Scholar 

  64. Yue M, Jiang J, Gao P, Liu H, Qing G. Oncogenic MYC activates a feedforward regulatory loop promoting essential amino acid metabolism and tumorigenesis. Cell Reports. 2017;21(13):3819–32.

    PubMed  CAS  Google Scholar 

  65. Keitaro H, Promsuk J, Hitoshi E, Naohiko A. c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells. Oncol Rep. 2012;28(3):862–6.

    Google Scholar 

  66. Yue M, Jiang J, Gao P, Liu H, Qing G. Oncogenic MYC activates a feedforward regulatory loop promoting essential amino acid metabolism and tumorigenesis. Cell Rep. 2017;21(13):3819–32.

    PubMed  CAS  Google Scholar 

  67. Han Li C, Chen Y. Targeting EZH2 for cancer therapy: progress and perspective. Curr Protein Pept Sci. 2015;16(6):559.

    PubMed  Google Scholar 

  68. Häfliger P, Charles R. The L-type amino acid transporter LAT1—an emerging target in cancer. Int J Mol Sci. 2019;20(10):2428.

    PubMed Central  Google Scholar 

  69. Yothaisong S, Dokduang H, Anzai N, Hayashi K, Namwat N, Yongvanit P, Sangkhamanon S, Jutabha P, Endou H, Loilome W. Inhibition of l-type amino acid transporter 1 activity as a new therapeutic target for cholangiocarcinoma treatment. Tumor Biol. 2017;39(3):1–14.

    Google Scholar 

  70. Cormerais Y, Giuliano S, LeFloch R, Front B, Durivault J, Tambutte E, Massard PA, de la Ballina LR, Endou H, Wempe MF, Palacin M, Parks SK, Pouyssegur J. 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. Cancer Res. 2016;76(15):4481–92.

    PubMed  CAS  Google Scholar 

  71. Yun DW, Lee SA, Park MG, Kim JS, Yu SK, Park MR, Kim SG, Oh JS, Kim CS, Kim HJ, Kim JS, Chun HS, Kanai Y, Endou H, Wempe MF, Kim DK. JPH203 (an L-type amino acid transporter 1-selective compound (induces apoptosis of YD-38 human oral cancer cells. J Pharmacol Sci. 2014;124(2):208–17.

    PubMed  CAS  Google Scholar 

  72. Choi DW, Kim DK, Kanai Y, Wempe MF, Endou H, Kim J. JPH203 (a selective L-type amino acid transporter 1 inhibitor (induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells. Korean J Physiol Pharmacol. 2017;21(6):599.

    PubMed  PubMed Central  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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Correspondence to Jun Ye.

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This study was funded by Taizhou People’s Hospital Medical Innovation Team Foundation (CXTDA201901, CXTDA201904) and the Taizhou People’s Hospital Mandatory Project (ZL201809).

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All authors (ZCM, XJ, XSS, and YJ) have declared that there is no conflict of interest.

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Zhang, C., Xu, J., Xue, S. et al. Prognostic Value of L-Type Amino Acid Transporter 1 (LAT1) in Various Cancers: A Meta-Analysis. Mol Diagn Ther 24, 523–536 (2020). https://doi.org/10.1007/s40291-020-00470-x

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