Exploration of new therapeutic strategy targeting amino acid transporter in renal cell carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18108
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Yamagata University
• Principal Investigator: Yamagishi Atsushi 山形大学, 医学部, 助教 (70571678)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: LAT1 / 4F2 / amino acid transpoter / renal cell carcinoma

Outline of Final Research Achievements

Comparison between human renal cell carcinoma cell line ACHN and rapamycin resistant ACHN (ACHN/RR) using metabolome analysis, most of amino acids were high level but glutamine was low level in ACHN/RR. In addition, the mRNA expressions of LAT1 and 4F2 were high, which form a dimer, transport amino acids intracellularly, and pump glutamine out of cell.
In ACHN, ACHN/RR, and other human renal cell carcinoma cell lines, the rapamycin susceptibility is low in cells with high expression of LAT1 and 4F2. However, knockdown of LAT1 or 4F2 did not enhance the susceptibility of rapamycin.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

現在までの研究で、LAT1、４F2がラパマイシン耐性のマーカーとなる可能性は示されているものの、臨床検体を用いてマーカーとなるかの検索はできていない。また、LAT1、４F2の阻害がラパマイシン耐性の克服に寄与する可能性を探索してきたが、本検討では否定的な結果となった。これまでの研究でLAT1、４F2の発現を制御している因子がラパマイシン耐性機序に関与していることが示唆されるため、LAT１、４F2の制御の観点から研究を継続する予定である。