更新于：2024-11-01

SLC1A4

更新于：2024-11-01

基本信息

别名

alanine/serine/cysteine/threonine transporter、Alanine/serine/cysteine/threonine transporter 1、ASCT-1

+ [6]

简介

Sodium-dependent neutral amino-acid transporter that mediates transport of alanine, serine, cysteine, proline, hydroxyproline and threonine.

关联

项与 SLC1A4 相关的药物

WO2024121126

专利挖掘

靶点

SLC1A4

作用机制-

在研机构

Institut National de la Santé et de la Recherche Médicale [+1]

原研机构

Institut National de la Santé et de la Recherche Médicale [+2]

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SLC1A4 相关的临床结果

登录后查看更多信息

100 项与 SLC1A4 相关的转化医学

登录后查看更多信息

0 项与 SLC1A4 相关的专利（医药）

登录后查看更多信息

200

项与 SLC1A4 相关的文献（医药）

2024-10-29·Proceedings of the National Academy of Sciences

Receptor usage of Syncytin-1: ASCT2, but not ASCT1, is a functional receptor and effector of cell fusion in the human placenta

Article

作者: Yang, Zhiqi ; Kučerová, Dana ; Trávníček, Martin ; Trejbalová, Kateřina ; Pecnová, Ľubomíra ; Salker, Madhuri S. ; Jech, Lukáš ; Hejnar, Jiří ; Janovská, Anna ; Štafl, Kryštof ; Stepanec, Vladimír

Syncytin-1, a human fusogenic protein of retroviral origin, is crucial for placental syncytiotrophoblast formation. To mediate cell-to-cell fusion, Syncytin-1 requires specific interaction with its cognate receptor. Two trimeric transmembrane proteins, Alanine, Serine, Cysteine Transporters 1 and 2 (ASCT1 and ASCT2), were suggested and widely accepted as Syncytin-1 cellular receptors. To quantitatively assess the individual contributions of human ASCT1 and ASCT2 to the fusogenic activity of Syncytin-1, we developed a model system where the ASCT1 and ASCT2 double knockout was rescued by ectopic expression of either ASCT1 or ASCT2. We demonstrated that ASCT2 was required for Syncytin-1 binding, cellular entry, and cell-to-cell fusion, while ASCT1 was not involved in this receptor interaction. We experimentally validated the ASCT1–ASCT2 heterotrimers as a possible explanation for the previous misidentification of ASCT1 as a receptor for Syncytin-1. This redefinition of receptor specificity is important for proper understanding of Syncytin-1 function in normal and pathological pregnancy.

2024-09-01·Redox Biology

Hypoxia-induced cysteine metabolism reprogramming is crucial for the tumorigenesis of colorectal cancer

Article

作者: Qiu, Qianqian ; Yin, Peng ; Sun, Longci ; Gu, Jun ; Li, Xiangyu ; Yang, Shiyi ; Hao, Yujun ; Lin, Zhang ; Zhang, Yanhua ; Chen, Chengkun ; Yao, Meilian ; Wang, Ting ; Cui, Gaoping

Metabolic reprogramming is a hallmark of human cancer, and cancer-specific metabolism provides opportunities for cancer diagnosis, prognosis, and treatment. However, the underlying mechanisms by which metabolic pathways affect the initiation and progression of colorectal cancer (CRC) remain largely unknown. Here, we demonstrate that cysteine is highly enriched in colorectal tumors compared to adjacent non-tumor tissues, thereby promoting tumorigenesis of CRC. Synchronously importing both cysteine and cystine in colorectal cancer cells is necessary to maintain intracellular cysteine levels. Hypoxia-induced reactive oxygen species (ROS) and ER stress regulate the co-upregulation of genes encoding cystine transporters (SLC7A11, SLC3A2) and genes encoding cysteine transporters (SLC1A4, SLC1A5) through the transcription factor ATF4. Furthermore, the metabolic flux from cysteine to reduced glutathione (GSH), which is critical to support CRC growth, is increased due to overexpression of glutathione synthetase GSS in CRC. Depletion of cystine/cysteine by recombinant cyst(e)inase effectively inhibits the growth of colorectal tumors by inducing autophagy in colorectal cancer cells through mTOR-ULK signaling axis. This study demonstrates the underlying mechanisms of cysteine metabolism in tumorigenesis of CRC, and evaluates the potential of cysteine metabolism as a biomarker or a therapeutic target for CRC.

2024-07-01·Molecular Pharmaceutics

Transporter Protein Expression of Corneal Epithelium in Rabbit and Porcine: Evaluation of Models for Ocular Drug Transport Study

Article

作者: Urtti, Arto ; Ramsay, Eva ; Terasaki, Tetsuya ; Kidron, Heidi ; Uchida, Yasuo ; Auriola, Seppo ; Montaser, Ahmed B. ; Niitsu, Kanako ; Huttunen, Kristiina M.

The transcorneal route is the main entry route for drugs to the intraocular parts, after topical administration. The outer surface, the corneal epithelium (CE), forms the rate-limiting barrier for drug permeability. Information about the role and protein expression of drug and amino acid transporter proteins in the CE is sparse and lacking. The aim of our study was to characterize transporter protein expression in rabbit and porcine CE to better understand potential drug and nutrient absorption after topical administration. Proteins, mainly Abc and Slc transporters, were characterized with quantitative targeted absolute proteomics and global untargeted proteomics methods. In the rabbit CE, 24 of 48 proteins were detected in the targeted approach, and 21 of these were quantified. In the porcine CE, 26 of 58 proteins were detected in the targeted approach, and 20 of these were quantified. Among these, 15 proteins were quantified in both animals: 4f2hc (Slc3a2), Aqp0, Asct1 (Slc1a4), Asct2 (Slc1a5), Glut1 (Slc2a1), Hmit (Slc2a13), Insr, Lat1 (Slc7a5), Mct1 (Slc16a1), Mct2 (Slc16a7), Mct4 (Slc16a3), Mrp 4 (Abcc4), Na⁺/K⁺-ATPase, Oatp3a1 (Slco3a1), and Snat2 (Slc38a2). Overall, the global proteomics results supported the targeted proteomics results. Organic anion transporting polypeptide Oatp3a1 was detected and quantified for the first time in both rabbit (1.4 ± 0.4 fmol/cm²) and porcine (11.1 ± 5.3 fmol/cm²) CE. High expression levels were observed for L-type amino acid transporter, Lat1, which was quantified with newly selected extracellular domain peptides in rabbit (48.9 ± 11.8 fmol/cm²) and porcine (37.6 ± 11.5 fmol/cm²) CE. The knowledge of transporter protein expression in ocular barriers is a key factor in the successful design of new ocular drugs, pharmacokinetic modeling, understanding ocular diseases, and the translation to human.