Targeting L-type amino acid transporter 1 in urological malignancy: Current status and future perspective
Targeting L-type amino acid transporter 1 in urological malignancy: Current status and future perspective
复制标题
泌尿系统恶性肿瘤中靶向 L 型氨基酸转运蛋白 1：现状和未来展望
DOI：
10.1016/j.jphs.2022.10.002
复制
发表时间：
2022
影响因子：
3.5
通讯作者：
Anzai Naohiko
中科院分区：
文献类型：
--
作者：
Pae Sangjon;Sakamoto Shinichi;Zhao Xue;Saito Shinpei;Tamura Takaaki;Imamura Yusuke;Sazuka Tomokazu;Reien Yoshie;Hirayama Yuri;Hashimoto Hirofumi;Kanai Yoshikatsu;Ichikawa Tomohiko;Anzai Naohiko
氨基酸转运体负责氨基酸的摄取，对细胞增殖至关重要。l型氨基酸转运体在必需氨基酸的摄取中起主要作用。l型氨基酸转运蛋白1 （LAT1）通过与4F2hc形成二聚体来发挥其功能特性。利用这种癌症特异性，针对LAT1的恶性肿瘤诊断影像学和治疗药物的研究在各个领域都取得了进展。在激素敏感的前列腺癌中，l型氨基酸转运蛋白3 （LAT3）通过雄激素受体（AR）上调。另一方面，在去势抵抗性前列腺癌中，已确定LAT1通过AR负向调节。此外，LAT1的结合伙伴4F2hc被确定为雄激素受体剪接变体7:AR-V7的特异性下游靶点。LAT1被认为有助于前列腺癌获得去势抵抗，使LAT1成为与抗雄激素和紫杉烷完全不同的治疗靶点。在肾癌和膀胱癌中也发现了LAT1表达的增加，这表明LAT1有助于恶性肿瘤的获得和进展。在日本，LAT1抑制剂治疗实体瘤的临床试验正在进行中，目前正在进行临床应用。本文就LAT1与泌尿系统恶性肿瘤的关系作一综述。
Amino acid transporters are responsible for the uptake of amino acids, critical for cell proliferation. L-type amino acid transporters play a major role in the uptake of essential amino acids. L-type amino acid transporter 1 (LAT1) exerts its functional properties by forming a dimer with 4F2hc. Utilizing this cancer-specificity, research on diagnostic imaging and therapeutic agents for malignant tumors targeting LAT1 progresses in various fields. In hormone-sensitive prostate cancer, the up-regulation of L-type amino acid transporter 3 (LAT3) through the androgen receptor (AR) has been identified. On the other hand, in castration-resistant prostate cancer, the negative regulation of LAT1 through AR has been determined. Furthermore, 4F2hc: a binding partner of LAT1, was identified as the specific downstream target of Androgen Receptor Splice Variant 7: AR-V7. LAT1 has been suggested to contribute to acquiring castration resistance in prostate cancer, making LAT1 a completely different therapeutic target from anti-androgens and taxanes. Increased expression of LAT1 has also been found in renal and bladder cancers, suggesting a contribution to acquiring malignancy and progression. In Japan, clinical trials of LAT1 inhibitors for solid tumors are in progress, and clinical applications are now underway. This article will summarize the relationship between LAT1 and urological malignancies.