Contribution of the L-Type Amino Acid Transporter Family in the Diagnosis and Treatment of Prostate Cancer

Author:

Zhao Xue1ORCID,Sakamoto Shinichi1ORCID,Wei Jiaxing1,Pae Sangjon12,Saito Shinpei12,Sazuka Tomokazu1,Imamura Yusuke1,Anzai Naohiko2,Ichikawa Tomohiko1ORCID

Affiliation:

1. Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan

2. Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan

Abstract

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.

Funder

Grant-in-Aid for Scientific Research

Japan China Sasakawa Medical Fellowship

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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