Slc1a1-KO Mouse

Slc1a1, also known as excitatory amino acid carrier 1 (EAAC1), is a sodium-dependent glutamate/cysteine transporter. It plays a central role in regulating neuronal glutathione (GSH) production, and is involved in processes like glutamate uptake, which limits excitotoxicity [4,5]. It also participates in cystine uptake and GSH biosynthesis in cancer cells, and is associated with various biological pathways related to cell metabolism and redox homeostasis [6].

In solid tumors, HIF-1α enhances the transcription of SLC1A1, promoting cystine uptake and ferroptosis resistance [1]. In IDH1-mutant solid tumors, SLC1A1 facilitates the influx of R-2-hydroxyglutarate into endothelial cells, promoting tumor angiogenesis [2]. In natural killer T-cell lymphoma, SLC1A1 promotes tumor growth by reprogramming glutamine metabolism, and its overexpression is associated with PD-L1 downregulation [3]. SLC1A1 deficiency in mice abolishes mIDH1-promoted tumor angiogenesis and the therapeutic benefit of mIDH1 inhibitor in solid tumors [2].

In conclusion, Slc1a1 is crucial for maintaining glutamate homeostasis, GSH production, and is involved in multiple disease-related processes. Mouse models with Slc1a1 deficiency have been instrumental in revealing its role in tumor angiogenesis and ferroptosis resistance in solid tumors, as well as its impact on lymphoma progression, thus providing insights into potential therapeutic strategies for these diseases.