Amino acid transporters overexpressed in tumors (AATs)

Amino acid transporters overexpressed in tumors represent a critical class of membrane proteins that facilitate the heightened nutrient demands of malignant cells. These transporters, primarily belonging to the solute carrier (SLC) family, include key members such as LAT1 (SLC7A5), ASCT2 (SLC1A5), and xCT (SLC7A11), which are frequently upregulated in response to oncogenic signaling from factors like c-Myc or HIF-1α. Their primary biological function is to import essential and conditionally essential amino acids to support rapid protein synthesis, energy production, and redox balance via glutathione production. By serving as nutrient gates, they also play a pivotal role in activating the mTORC1 signaling pathway, a master regulator of cell growth and metabolism. Therapeutic strategies targeting these transporters, such as the LAT1 inhibitor JPH203 or the ASCT2 inhibitor V-9302, aim to starve cancer cells of vital nutrients, leading to growth arrest or cell death. Additionally, their high expression levels make them effective targets for diagnostic imaging using radiolabeled amino acids, though challenges remain regarding the potential for off-target effects in healthy tissues with high metabolic activity.

Other names

Tumor-associated amino acid transportersSolute carrier amino acid transportersSLC transporters in cancerLarge neutral amino acid transporter 1 (LAT1)Alanine, serine, cysteine-preferring transporter 2 (ASCT2)Cystine/glutamate antiporter (xCT)SLC7A5SLC1A5SLC7A11

Inhibition of amino acid uptake leading to nutrient deprivation, suppression of mTORC1 signaling, and induction of oxidative stress or ferroptosis.