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Solute carrier family 6 member 14 (SLC6A14), commonly known as ATB0+, is a Na+ and Cl- dependent transporter that mediates the concentrative uptake of 18 of the 20 proteinogenic amino acids, excluding only the acidic ones (aspartate and glutamate) [1, 5]. It is uniquely characterized by its broad substrate specificity and high concentrative capacity, which allows it to accumulate amino acids up to 1000-fold within cells, making it an ideal nutrient source for rapidly proliferating cells [1, 5, 9]. While expressed at low levels in most normal tissues, it is significantly upregulated in various solid tumors, including pancreatic, colorectal, cervical, and estrogen receptor-positive breast cancers [1, 3, 4, 11]. In these malignancies, ATB0+ acts as a "nutrient pump" that fuels the mTOR signaling pathway and supports metabolic reprogramming [4, 10]. Pharmacological blockade of the transporter, such as with the inhibitor alpha-methyl-DL-tryptophan, induces amino acid starvation, inhibits mTOR, and promotes autophagy or apoptosis in cancer cells [4, 8, 11]. Additionally, its ability to transport amino acid-based prodrugs makes it a promising vehicle for targeted delivery of chemotherapeutic agents [6, 13].
Inhibition of amino acid transport leading to intracellular amino acid depletion, suppression of the mTOR signaling pathway, and induction of autophagy and apoptosis.
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