Alanine-serine-cysteine transporter system (ASCT) (ASCT)

The Alanine-serine-cysteine transporter (ASCT) system, primarily comprising the SLC1A4 (ASCT1) and SLC1A5 (ASCT2) transporters, mediates the sodium-dependent exchange of small neutral amino acids across cell membranes (Broer, 2014). While ASCT1 primarily transports alanine, serine, and cysteine, ASCT2 is distinguished by its high affinity for glutamine, making it a critical regulator of glutamine homeostasis in rapidly proliferating cells (UniProt Consortium, 2024). In many cancers, ASCT2 is significantly upregulated to meet the increased demand for glutamine, which fuels the TCA cycle and activates the mTORC1 signaling pathway to promote cell growth and survival (Scalise et al., 2018). Consequently, the ASCT system, particularly ASCT2, has emerged as a prominent therapeutic target for glutamine-addicted tumors (Schulte et al., 2018). Pharmacological inhibition of these transporters, using small molecules like V-9302, aims to induce nutrient stress, oxidative damage, and apoptosis in malignant cells (Schulte et al., 2018). However, therapeutic development must account for the system's role in normal physiological processes, such as neurotransmitter regulation and immune cell function (Broer, 2014; Nakaya et al., 2014).

Other names

System ASCNeutral amino acid transporterSLC1A4 and SLC1A5ASCT1 and ASCT2

Competitive inhibition of neutral amino acid uptake (primarily glutamine via ASCT2), which triggers nutrient stress, inhibits mTORC1 signaling, increases reactive oxygen species, and induces apoptosis (Schulte et al., 2018).