Prevention of tumor development by elucidation of function of amino acids

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H04123
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kobe University
• Principal Investigator: Hoshi Namiko 神戸大学, 医学部附属病院, 講師 (40645214)
• Co-Investigator(Kenkyū-buntansha): 佐々木 大介 神戸大学, 科学技術イノベーション研究科, 特命助教 (00650615) ; 佐々木 建吾 神戸大学, 科学技術イノベーション研究科, 客員准教授 (50558301)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アミノ酸 / 腸管腫瘍 / 予防

Outline of Final Research Achievements

Colorectal cancer has increased during a few decades after the World War II, it is now ranked first among women and third among men in terms of cancer mortality. Epidemiologically, consumption of red and processed meat has been identified as risk factors, suggesting the importance of environmental factors such as nutritional status in addition to genetic factors, but the mechanism is not yet clarified.
In this project, we decided to investigate the role of amino acids, the major nutrients in meat, in intestinal tumorigenesis. As an approach, we focused on L-type amino acid transporter-1 (LAT1), a transporter of many essential amino acids, and found that LAT1 is required for normal small intestinal epithelial differentiation and that LAT1 deficiency affects small intestinal tumorigenesis. The findings were presented at domestic and international conferences　and published in a literature.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

LAT1は、本課題開始当初、大腸癌細胞特異的に発現し腫瘍増殖に寄与すると考えられていたが詳細な機能は不明であった。そこで、腸管上皮でのみLAT1が欠損する腫瘍モデルマウスを作成し解析した。結果として、想定外にもLAT1は正常陰窩上皮で恒常的に発現し、LAT1欠損でパネート細胞数が激減することを見出した。LAT1欠損は腫瘍径の減少だけでなく発生数も有意に抑制することを観察し、パネート細胞が分泌するWnt3蛋白の産生減少が関わることが示唆された。栄養素と腫瘍発生の関わりを示す基礎研究結果であり、食生活からの大腸がん予防法の開発など社会還元に発展させることが期待できる有意義な成果と考える。