The Pathological Roles of Cationic Amino Acid Transporters (CATs) in Cancer.

Cationic amino acid transporters (CATs), encoded by the SLC7A family, play essential roles in the uptake of arginine and other cationic amino acids, thereby regulating cellular metabolism, signaling, and immune responses. Among SLC7A transporters, SLC7A1-4 constitute the classical CAT family and have emerged as important regulators of tumor biology. Arginine is increasingly recognized as a critical metabolic resource within the tumor microenvironment. Consequently, dysregulated CAT expression can affect both cancer cell fitness and tumor-immune interactions. In this review, we summarize current knowledge regarding the biological and pathological roles of SLC7A1-4 in cancer. SLC7A1 is broadly associated with enhanced tumor growth, metabolic adaptation, and therapeutic resistance through increased arginine uptake. In contrast, SLC7A2 exhibits context-dependent functions, displaying both tumor-promoting and tumor-suppressive activities depending on tumor type and immune context regulation. Emerging evidence also implicates SLC7A3 in metastatic progression through transcriptional programs that increase arginine availability, whereas the physiological role of SLC7A4 remains largely unresolved. Despite its structural similarity to other CAT family members, convincing evidence for its membrane localization, cationic amino acid transport activity, and cancer-associated functions is still lacking. We further discuss the mechanistic pathways linking CAT to cancer progression and tumor-immune metabolic competition. Finally, we highlight key unresolved questions, including functional redundancy among CAT family members, context-dependent biological effects, and the uncertain role of SLC7A4. A deeper understanding of CAT biology may provide new opportunities for therapeutic strategies targeting amino acid metabolism in cancer.