mTOR signaling mechanisms dependent on amino acid transporter

• Project/Area Number: 25860189
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kyoto Prefectural University of Medicine (2014); Osaka University (2013)
• Principal Investigator: TADAGAKI KENJIRO 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30416268)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 薬理学 / シグナル伝達 / アミノ酸トランスポーター / トランスポーター

Outline of Final Research Achievements

We performed this study to elucidate the signaling mechanisms leading to mTOR via L-type amino acid transporter (LAT1) by means of comprehensive phosphoproteomics and LAT1 inhibitors, revealing the overview of cellular responses mediated by LAT1 and to examine the possibilities of LAT1 as a molecular marker for cancer therapy. We found that the leucine uptake by LAT1 not only controls the phosphorylated proteins related to the translation regulations but induces the protein phosphorylations responsible for various cellular responses such as transcription, cell cycle regulation and cell structures. Our results indicated that co-administration of known anti-cancer agents with LAT1 inhibitors may be useful for cancer therapy.

Research Products

• [Presentation] Inhibition of cancer-type amino acid transporter LAT1 affects multiple cellular events in pancreatic cancer cells. (2014)
  • Author(s): Pornparn Kongprach, Pattama Wiriyasermkul, Noriyoshi Isozumi, Printip Wongthai, Suguru Okuda, Kenjiro Tadagaki, Ryuichi Ohgaki, Shushi Nagamori, Yoshikatsu Kanai
  • Organizer: The 126th Meeting of Japanese Pharmacological Society Kinki Branch
  • Place of Presentation: 和歌山県JAビル（ 和歌山市 ）
  • Year and Date: 2014-10-24
• [Presentation] Study of a cellular signaling network stimulated with leucine transported by a cancer-type amino acid transporter LAT1. (2014)
  • Author(s): Pornparn Kongprach, Pattama Wiriyasermkul, Noriyoshi Isozumi, Printip Wongthai, Suguru Okuda, Kenjiro Tadagaki, Ryuichi Ohgaki, Shushi Nagamori, Yoshikatsu Kanai
  • Organizer: The 61th Japanese Biochemical Society Kinki Branch
  • Place of Presentation: 京都産業大学（ 京都市北区 ）
  • Year and Date: 2014-05-17
• [Presentation] Transport mechanisms of 4-borono-phenylalanine as a 10B carrier of boron neutron capture therapy for cancers. (2014)
  • Author(s): Printip Wongthai, Kohei Hagiwara, Yurika Miyoshi, Pattama Wiriyasermkul, Pornparn Kongpracha, Isozumi Noriyoshi1, Ryuichi Ohgaki, Kenjiro Tadagaki, Kenji Hamase, Shushi Nagamori, Yoshikatsu Kanai
  • Organizer: The 61th Japanese Biochemical Society Kinki Branch
  • Place of Presentation: 京都産業大学（ 京都市北区 ）
  • Year and Date: 2014-05-17