Slc1a3, also known as a glutamate transporter, is a member of the solute carrier family 1. It plays a crucial role in regulating the transport of aspartate and glutamate, which are important for maintaining normal cellular metabolism and neurotransmission. It is mainly expressed in brain tissues but also shows high expression in some tumor types. Its associated pathways may include those related to glutamine catabolism, PI3K/AKT signaling, and immune-related processes, and it is of great biological importance in normal physiological and disease-related contexts [2,3,5].

In terms of disease-related findings, knockdown of Slc1a3 inhibits Newcastle disease virus (NDV) infection, as it is hijacked by NDV to regulate glutamine catabolism for efficient viral replication [1]. In solid tumors, inhibition of Slc1a3 in combination with L-asparaginase (ASNase) causes cell cycle arrest or apoptosis, suggesting its role in ASNase resistance [2]. In gastric cancer, Slc1a3 overexpression promotes cancer growth via the PI3K/AKT signaling pathway [3]. High expression of Slc1a3 in ovarian cancer is associated with poor prognosis, and its knockdown restrains cell proliferation, enhances apoptosis, and inhibits migration [7]. Additionally, Slc1a3 may be implicated in hemiplegic migraine [4,6].

In conclusion, Slc1a3 is essential for regulating amino acid transport and metabolism. Functional studies, especially through knockdown experiments, have revealed its significant roles in viral replication, cancer progression, and potentially in neurological disorders like hemiplegic migraine. These findings provide important insights into the underlying mechanisms of these diseases and suggest Slc1a3 as a potential therapeutic target.

References:

1. Liu, Panrao, Tang, Ning, Meng, Chunchun, Lin, Shu-Hai, Ding, Chan. . SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism. In Virulence, 13, 1407-1422. doi:10.1080/21505594.2022.2112821. https://pubmed.ncbi.nlm.nih.gov/35993169/

2. Sun, Jianhui, Nagel, Remco, Zaal, Esther A, Berkers, Celia R, Agami, Reuven. 2019. SLC1A3 contributes to L-asparaginase resistance in solid tumors. In The EMBO journal, 38, e102147. doi:10.15252/embj.2019102147. https://pubmed.ncbi.nlm.nih.gov/31523835/

3. Xu, Liyi, Chen, Jiamin, Jia, Litao, Awaleh Moumin, Faycal, Cai, Jianting. 2020. SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. In Journal of cellular and molecular medicine, 24, 14392-14404. doi:10.1111/jcmm.16060. https://pubmed.ncbi.nlm.nih.gov/33145952/

4. Nandyala, Arathi, Shah, Tulsi, Ailani, Jessica. 2023. Hemiplegic Migraine. In Current neurology and neuroscience reports, 23, 381-387. doi:10.1007/s11910-023-01277-z. https://pubmed.ncbi.nlm.nih.gov/37247170/

5. Zhi, Renhou, Fan, Fan. 2024. SLC1A3 is a novel prognostic biomarker associated with immunity and EMT in hepatocellular carcinoma. In Discover oncology, 15, 676. doi:10.1007/s12672-024-01561-5. https://pubmed.ncbi.nlm.nih.gov/39560677/

6. Paucar, Martin, Granberg, Tobias, Lagerstedt-Robinson, Kristina, Nordin, Love, Svenningsson, Per. 2020. SLC1A3 variant associated with hemiplegic migraine and acetazolamide-responsive MRS changes. In Neurology. Genetics, 6, e474. doi:10.1212/NXG.0000000000000474. https://pubmed.ncbi.nlm.nih.gov/32754645/

7. Zhou, Wu, Xiong, Yanqiang, Zhao, Liangping, Liu, Zhihui, Ma, Yuanxue. 2024. SLC1A3 knockdown in inhibiting the proliferation, apoptosis resistance, and migration of ovarian cancer cells. In Translational cancer research, 13, 6315-6322. doi:10.21037/tcr-24-1909. https://pubmed.ncbi.nlm.nih.gov/39697758/