Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Int J Mol Sci. 2023 Mar 24;24(7):6178. doi: 10.3390/ijms24076178.
The L-type amino acid transporter (LAT) family contains four members, LAT1~4, which are important amino acid transporters. They mainly transport specific amino acids through cell membranes, provide nutrients to cells, and are involved in a variety of metabolic pathways. They regulate the mTOR signaling pathway which has been found to be strongly linked to cancer in recent years. However, in the field of prostate cancer (PCa), the LAT family is still in the nascent stage of research, and the importance of LATs in the diagnosis and treatment of prostate cancer is still unknown. Therefore, this article aims to report the role of LATs in prostate cancer and their clinical significance and application. LATs promote the progression of prostate cancer by increasing amino acid uptake, activating the mammalian target of rapamycin (mTOR) pathway and downstream signals, mediating castration-resistance, promoting tumor angiogenesis, and enhancing chemotherapy resistance. The importance of LATs as diagnostic and therapeutic targets for prostate cancer was emphasized and the latest research results were introduced. In addition, we introduced selective LAT1 inhibitors, including JPH203 and OKY034, which showed excellent inhibitory effects on the proliferation of various tumor cells. This is the future direction of amino acid transporter targeting therapy drugs.
L 型氨基酸转运体(LAT)家族包含四个成员,LAT1~4,它们是重要的氨基酸转运体。它们主要通过细胞膜转运特定的氨基酸,为细胞提供营养,并参与多种代谢途径。它们调节 mTOR 信号通路,近年来发现该通路与癌症密切相关。然而,在前列腺癌(PCa)领域,LAT 家族仍处于研究的萌芽阶段,LATs 在前列腺癌的诊断和治疗中的重要性尚不清楚。因此,本文旨在报告 LATs 在前列腺癌中的作用及其临床意义和应用。LATs 通过增加氨基酸摄取、激活哺乳动物雷帕霉素靶蛋白(mTOR)通路及其下游信号、介导去势抵抗、促进肿瘤血管生成和增强化疗耐药性来促进前列腺癌的进展。强调了 LATs 作为前列腺癌诊断和治疗靶点的重要性,并介绍了最新的研究结果。此外,我们还介绍了选择性 LAT1 抑制剂,包括 JPH203 和 OKY034,它们对各种肿瘤细胞的增殖表现出优异的抑制作用。这是氨基酸转运体靶向治疗药物的未来方向。