Neutral amino acid transporter B(0) (SLC1A5) (ASCT2)

Neutral amino acid transporter B(0) (SLC1A5), commonly known as ASCT2, is a sodium-dependent neutral amino acid exchanger that plays a pivotal role in cellular nutrient uptake, particularly glutamine (UniProt: P46459). It is essential for maintaining intracellular amino acid pools and serves as a key upstream activator of the mTORC1 signaling pathway, which coordinates cell growth and protein synthesis (PubMed: 29626011). In many cancers, ASCT2 is overexpressed to support the high metabolic demands of rapidly proliferating cells, a phenomenon often termed "glutamine addiction" (PubMed: 30115704). This overexpression makes it a significant therapeutic target in various malignancies, including triple-negative breast cancer and non-small cell lung cancer (PubMed: 25605020). Pharmacological targeting of ASCT2, such as with the small-molecule inhibitor V-9302, has demonstrated the ability to induce oxidative stress and inhibit tumor growth in preclinical models (PubMed: 29626011). Additionally, ASCT2 functions as the primary cell-surface receptor for several retroviruses, including the RD114 virus and feline leukemia virus subgroup B (PubMed: 10400744). Therapeutic challenges include the potential for toxicity in normal tissues like the gut and the immune system, which also rely on glutamine transport (PubMed: 30115704).

Other names

SLC1A5Solute carrier family 1 member 5Alanine/serine/cysteine-preferring transporter 2ATB(0)AAATM7V1RDRC

Inhibition of sodium-dependent neutral amino acid transport, specifically blocking the uptake of glutamine to starve cancer cells and inhibit mTORC1 signaling.