Expression of L-type amino acid transporter 1 is a poor prognostic factor for Non-Hodgkin's lymphoma.
Expression of L-type amino acid transporter 1 is a poor prognostic factor for Non-Hodgkin's lymphoma.
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DOI：
10.1038/s41598-021-00811-8
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发表时间：
2021-11-04
影响因子：
4.6
通讯作者：
Kuroda M
中科院分区：
文献类型：
--
作者：
Jigjidkhorloo N;Kanekura K;Matsubayashi J;Akahane D;Fujita K;Oikawa K;Kurata A;Takanashi M;Endou H;Nagao T;Gotoh A;Norov O;Kuroda M
L型中性氨基酸转运蛋白1（LAT1）是一种异源二聚体膜转运蛋白，参与中性氨基酸的转运。LAT1在多种恶性实体瘤中高度表达，并在细胞增殖中起重要作用。然而，其在恶性淋巴瘤中的作用仍然未知。在这里，我们评估了138例非霍奇金淋巴瘤（NHL）患者组织中的LAT1表达水平。在所有类型的NHL中都证实了LAT1的过表达，并且我们发现LAT1的表达水平与淋巴瘤分级之间存在显著相关性。与静止型淋巴瘤相比，LAT1在侵袭型淋巴瘤中的表达更高，表明活跃的肿瘤增殖需要通过LAT1摄取营养。LAT1的表达水平与患者的生存期呈负相关。此外，通过特异性抑制剂JPH 203对LAT1的药理学抑制抑制淋巴瘤细胞生长。总之，我们的研究表明，LAT1表达可用作NHL患者的预后标志物，并且通过JPH 203靶向LAT1可以成为NHL的新治疗方式。
L-type neutral amino acid transporter 1 (LAT1) is a heterodimeric membrane transport protein involved in neutral amino acid transport. LAT1 is highly expressed in various malignant solid tumors and plays an essential role in cell proliferation. However, its role in malignant lymphoma remains unknown. Here, we evaluated LAT1 expression level in tissues from 138 patients with Non-Hodgkin lymphoma (NHL). Overexpression of LAT1 was confirmed in all types of NHL and we found that there is a significant correlation between the level of LAT1 expression and lymphoma grade. The LAT1 expression was higher in aggressive types of lymphomas when compared with static types of lymphomas, suggesting that active tumor proliferation requires nutrient uptake via LAT1. The expression level of LAT1 was inversely correlated with patients’ survival span. Furthermore, pharmacological inhibition of LAT1 by a specific inhibitor JPH203 inhibits lymphoma cell growth. In conclusion, our study demonstrated that LAT1 expression can be used as a prognostic marker for patients with NHL and targeting LAT1 by JPH203 can be a novel therapeutic modality for NHL.
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影响因子：
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通讯作者：
Mori, M.
影响因子：
4
作者：
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Murakumo, Yoshiki
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通讯作者：
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10.3
作者：
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通讯作者：
Holst, Jeff
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影响因子：
4
作者：
Dong, Huan;Wang, Qiang;Guo, Xiangqian
通讯作者：
Guo, Xiangqian