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L型氨基酸转运体1通过mTORC1促进人绒毛膜滋养层细胞和绒毛膜癌细胞的增殖与侵袭。

L-type amino acid transporter 1 promotes proliferation and invasion of human chorionic trophoblast and choriocarcinoma cells through mTORC1.

作者信息

Luo Wenping, Zhang Hongmei, Zhang Yan, Liang Panpan, Wang Xiaojie, Ma Jing, Tan Dongmei, Tan Yi, Song Jinlin, Ji Ping, Zhao Tianyu

机构信息

Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences 426 Songshi North Road, Yubei Distrinct, Chongqing 401147, China.

Stomatological Hospital of Chongqing Medical University 426 Songshi North Road, Yubei Distrinct, Chongqing 401147, China.

出版信息

Am J Transl Res. 2020 Oct 15;12(10):6665-6681. eCollection 2020.

PMID:33194063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7653574/
Abstract

L-type amino acid transporter 1 (LAT1) is a neutral amino acid transporter expressed in trophoblast giant cells onembryonic day 8 in mice. LAT1 is responsible for metabolism in blastocysts and cancer cells. Despite research concerning the aberrant high expression and indispensable function of LAT1 in various cancers, little is known about the role of LAT1 in regulating the behaviors of human trophoblast cells under different physiological and pathological conditions. The HTR8-SVneo human trophoblast cell line and JEG-3 and JAR choriocarcinoma cell lines are used as models for trophoblast cell biological research. The proliferation and apoptosis of these cells were assayed using the CCK-8 assay and flow cytometry, respectively. Transwell-chambers were used to observed migration and invasion of the cells. Immunofluorescent staining, western blot, and RT-PCR assays were used to determine the possible mechanism of LAT1 on human trophoblast cell behaviors with small interfering RNA or signal agonists and antagonist treatments. LAT1 was expressed in the trophoblast and choriocarcinoma cells. LAT1 was involved in regulating behaviors of these cells, such as cell proliferation, apoptosis, migration, and invasion. Detailed results suggested that LAT1 modulated trophoblast cell functions by mediation of mTORC1 signaling pathways. Our results implicate LAT1 as a very important regulator in human trophoblast cell behaviors at the maternal-fetal interface.

摘要

L型氨基酸转运体1(LAT1)是一种在小鼠胚胎第8天的滋养层巨细胞中表达的中性氨基酸转运体。LAT1负责胚泡和癌细胞的代谢。尽管已有关于LAT1在各种癌症中异常高表达及不可或缺功能的研究,但对于LAT1在不同生理和病理条件下调节人滋养层细胞行为的作用却知之甚少。HTR8-SVneo人滋养层细胞系以及JEG-3和JAR绒毛膜癌细胞系被用作滋养层细胞生物学研究的模型。分别使用CCK-8法和流式细胞术检测这些细胞的增殖和凋亡。采用Transwell小室观察细胞的迁移和侵袭。通过小干扰RNA或信号激动剂及拮抗剂处理,利用免疫荧光染色、蛋白质印迹法和逆转录-聚合酶链反应检测来确定LAT1对人滋养层细胞行为的可能机制。LAT1在滋养层细胞和绒毛膜癌细胞中表达。LAT1参与调节这些细胞的行为,如细胞增殖、凋亡、迁移和侵袭。详细结果表明,LAT1通过mTORC1信号通路的介导来调节滋养层细胞功能。我们的结果表明LAT1是母胎界面人滋养层细胞行为的一个非常重要的调节因子。

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本文引用的文献

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Positive regulation of placentation by L-amino acid transporter-1 (lat1) in pregnant mice.L-氨基酸转运体-1(Lat1)对妊娠小鼠胎盘形成的正向调节作用
Int J Clin Exp Pathol. 2017 Sep 1;10(9):9551-9558. eCollection 2017.
2
Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.人源 LAT1-4F2hc 异型氨基酸转运体复合物的结构。
Nature. 2019 Apr;568(7750):127-130. doi: 10.1038/s41586-019-1011-z. Epub 2019 Mar 13.
3
New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma.新型氟乙基苯丙氨酸类似物作为潜在的 LAT1 靶向脑胶质瘤正电子发射断层扫描(PET)示踪剂。
Sci Rep. 2019 Feb 27;9(1):2878. doi: 10.1038/s41598-019-40013-x.
4
The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model.LAT1 抑制剂 JPH203 可降低完全免疫活性小鼠模型中甲状腺癌的生长。
J Exp Clin Cancer Res. 2018 Sep 21;37(1):234. doi: 10.1186/s13046-018-0907-z.
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Structure of the human plasma membrane Ca-ATPase 1 in complex with its obligatory subunit neuroplastin.人血浆膜 Ca-ATPase 1 与其必需亚基神经钙蛋白复合物的结构。
Nat Commun. 2018 Sep 6;9(1):3623. doi: 10.1038/s41467-018-06075-7.
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The Human SLC7A5 (LAT1): The Intriguing Histidine/Large Neutral Amino Acid Transporter and Its Relevance to Human Health.人类溶质载体家族7成员5(LAT1):引人入胜的组氨酸/大型中性氨基酸转运体及其与人类健康的关联。
Front Chem. 2018 Jun 22;6:243. doi: 10.3389/fchem.2018.00243. eCollection 2018.
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