Neutral amino acid transporter ASCT2 (SLC1A5) (SLC1A5)

SLC1A5 (Solute Carrier Family 1 Member 5), commonly known as ASCT2, is a sodium-dependent neutral amino acid transporter that plays a pivotal role in cellular metabolism by mediating the uptake of glutamine (UniProt P43007). The SLC1A5 mRNA is highly expressed in numerous cancer types, where it facilitates glutamine addiction, a metabolic state where tumor cells rely on exogenous glutamine for energy production, nucleotide synthesis, and redox balance (PubMed: 29626121). By regulating intracellular glutamine levels, SLC1A5 also acts as a key upstream activator of the mTORC1 signaling pathway, which coordinates cell growth and proliferation in response to nutrient availability (PubMed: 16168377). Therapeutic targeting of SLC1A5 mRNA via RNA interference (siRNA) or antisense oligonucleotides (ASOs) aims to deplete the ASCT2 protein, thereby inhibiting tumor growth and sensitizing cells to other therapies (PubMed: 30104678). Small molecule inhibitors like V-9302 have also been developed to target the protein product, demonstrating significant anti-tumor activity in preclinical models (PubMed: 29626121). Beyond its role in oncology, SLC1A5 serves as a receptor for several subfamilies of type D retroviruses, including the Mason-Pfizer monkey virus (PubMed: 10400744). Monitoring SLC1A5 expression levels or using glutamine-based PET imaging serves as a potential biomarker strategy for identifying patients likely to benefit from SLC1A5-targeted interventions. However, safety concerns remain regarding the potential impact on normal tissues that depend on glutamine, such as the intestinal epithelium and activated immune cells (PubMed: 28423440).

Other names

ASCT2ATBOM7V1AAATRDRCSolute carrier family 1 member 5

Inhibition of neutral amino acid transport and reduction of protein expression through mRNA degradation or translational blockade