Solute carrier family 6 member 14 (SLC6A14): Expression, function, regulation, and impact on tumor progression.

Solute carrier family 6 member 14 (SLC6A14/ATB0,+) is a broad-spectrum, Na+/Cl--dependent amino acid transporter. It mediates the active uptake of nearly all essential amino acids and serves as a critical metabolic hub under physiological and pathological conditions. To fully understand its potential as a therapeutic target for cancer intervention, this review systematically elucidates the structural biology, regulatory networks, and multifaceted roles of SLC6A14 in cancer. By examining the expression patterns of SLC6A14 in physiological and pathological situation, we demonstrate that it's significantly upregulated in various "amino acid-dependent" malignancies.

It includes pancreatic cancer, colorectal cancer, and estrogen receptor-positive breast cancer, where it drives multiple signaling pathways and promotes tumor progression through diverse mechanisms. Beyond its classical metabolic functions, SLC6A14-mediated nutrient deprivation establishes a "nutrient-based immune evasion" mechanism, elucidating its potential for intervention in tumor immunity.

Furthermore, we outline a dual-pronged therapeutic strategy for SLC6A14, including its use as a target for pharmacological inhibition and as a delivery channel for amino acid-conjugated prodrugs. Finally, we emphasize that successful clinical translation requires a shift from biomarker-driven patient stratification to mechanism-driven implementation. This highlights the central role of SLC6A14 as an intervenable target at the intersection of cancer metabolism, immune regulation, and targeted therapy.