Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy

Solute carrier (SLC), a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment. Amino acids are fundamental building blocks of cells, playing essential roles not only in protein synthesis but also in nutrient sensing, and in signaling pathways that can promote tumorigenesis. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. Amino acid uptake by SLCs positively affects tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although a body of studies evaluated the function of SLC7A11 and SLC1A5, some of the SLC proteins are not studied sufficiently in cancer. In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids, as one of the most important materials that cancer cells need, and their transporters within the SLC superfamily.