The significance of the amino acid transporter as a cancer therapeutic targets as well as therapeutic effect predictive marker

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07755
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagoya City University
• Principal Investigator: Tetsuya Oguri 名古屋市立大学, 医薬学総合研究院(医学), 教授 (60363925)
• Co-Investigator(Kenkyū-buntansha): 前野 健 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (10444952)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: LAT1 / mTOR

Outline of Final Research Achievements

Among amino acid transporters, we focused on L-type amino acid transporter1（LAT1）and investigated about the role and its inhibitory effect in cancer cells, by using lung cancer cells. We examined the inhibitory effects of LAT1, and found cell growth inhibition in cancer cells. After treatment of LAT1 antibody, the mTOR pathway was activated, which is a downstream signal, however also re-elevated LAT1 expression by feedback from the mTOR pathway. The combined use of LAT1 antibody and mTOR inhibitor did not show further cell growth inhibitory effects. Although LAT1 is a candidate cancer therapeutic target, further examination is necessary to clarify the factors involved in amino acid metabolic reprogramming is required.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

がん細胞の増殖においてアミノ酸取り込みにLAT1が関与し、その阻害で増殖抑制につながることは明らかであるが、細胞内の増殖に関わるシグナルに関しては、LAT1の抑制のみでは困難なため、LAT1のみをターゲットとした治療戦略が、特に肺癌では難しいと思われる。このため、アミノ酸代謝にターゲットとした治療戦略を考える場合、がん細胞におけるアミノ酸代謝のリプログラミングに関わる因子や併用治療のさらなる検討が必要であると考えられた。