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

L型氨基酸转运蛋白1通过mTORC1促进人绒毛膜滋养层细胞和绒毛膜癌细胞增殖和侵袭

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

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.

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