Regulation of cellular metabolism and functions mediated by amino acid transporters and the mechanisms of action of their inhibitors

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04685
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: KANAI Yoshikatsu 大阪大学, 医学系研究科, 教授 (60204533)
• Co-Investigator(Kenkyū-buntansha): 永森 收志 大阪大学, 医学系研究科, 准教授 (90467572) ; 大垣 隆一 大阪大学, 医学系研究科, 助教 (20467525) ; 奥田 傑 大阪大学, 医学系研究科, 助教 (50511846) ; 中込 咲綾 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (60423894)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: トランスポーター / 受容体 / シグナル伝達系 / 細胞代謝制御 / 抗腫瘍薬

Outline of Final Research Achievements

Amino acid transporter LAT1 (L-type amino acid transporter 1) is highly upregulated in various types of cancer. LAT1 is known to supply cancer cells with most of the essential amino acids, thereby supporting the rapid cell growth and proliferation. By using newly developed LAT1-selective inhibitor, we tried to understand the functions of amino acids as signaling molecules, and to reveal the cellular metabolisms and other cellular functions regulated by amino acids transported by LAT1, especially leucine. Phosphoproteomics analysis revealed amino acid signaling in the downstream of LAT1. We also demonstrated relationships between LAT1 with tumor angiogenesis and metastasis. This research revealed novel functional aspects of the amino acid transporter and amino acid signaling. The results obtained also contributed to the comprehensive understanding of the mechanisms of action of LAT1 inhibitors as a novel class of anti-cancer agents.

Free Research Field

薬理学