Contribution of LAT1-4F2hc in Urological Cancers via Toll-like Receptor and Other Vital Pathways

SIMPLE SUMMARY: LAT1-4F2hc complex is an important amino acid transporter. It mainly transports specific amino acids through the cell membrane, provides nutrition for cells, and participates in a variety of metabolic pathways. LAT1 plays a role in transporting essential amino acids including leucine, which regulates the mTOR signaling pathway. However, the importance of SLCs is still not well known in the field of urological cancer. Therefore, the purpose of this review is to report the role of the LAT1-4F2hc complex in urological cancers, as well as their clinical significance and application. Moreover, the inhibitor of LAT1-4F2hc complex is a promising direction as a targeted therapy to improve the treatment and prognosis of urological cancers. ABSTRACT: Tumor cells are known for their ability to proliferate. Nutrients are essential for rapidly growing tumor cells. In particular, essential amino acids are essential for tumor cell growth. Tumor cell growth nutrition requires the regulation of membrane transport proteins. Nutritional processes require amino acid uptake across the cell membrane. Leucine, one of the essential amino acids, has recently been found to be closely associated with cancer, which activate mTOR signaling pathway. The transport of leucine into cells requires an L-type amino acid transporter protein 1, LAT1 (SLC7A5), which requires the 4F2 cell surface antigen heavy chain (4F2hc, SLC3A2) to form a heterodimeric amino acid transporter protein complex. Recent evidence identified 4F2hc as a specific downstream target of the androgen receptor splice variant 7 (AR-V7). We stressed the importance of the LAT1-4F2hc complex as a diagnostic and therapeutic target in urological cancers in this review, which covered the recent achievements in research on the involvement of the LAT1-4F2hc complex in urinary system tumors. In addition, JPH203, which is a selective LAT1 inhibitor, has shown excellent inhibitory effects on the proliferation in a variety of tumor cells. The current phase I clinical trials of JPH203 in patients with biliary tract cancer have also achieved good results, which is the future research direction for LAT1 targeted therapy drugs.