The role of ADAM17 in obesity-associated associated tumorigenesis

• Project/Area Number: 17K10651
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: OKABAYASHI Koji 慶應義塾大学, 医学部(信濃町), 講師 (00338063)
• Co-Investigator(Kenkyū-buntansha): 長谷川 博俊 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (00218455) ; 鶴田 雅士 慶應義塾大学, 医学部(信濃町), 講師 (00348666)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 大腸癌 / 発がん / 肥満 / ADAM17 / TNF-α / 癌 / 発癌

Outline of Final Research Achievements

In obese mice fed a high-fat diet, ADAM17 expression was enhanced in the large intestine mucosa. Furthermore, the expression of Chemokine ligand 14 (CXCL14), which inactivates ADAM17, was decreased in obese mice. In the obese environment, the activity of CXCL14 is decreased, and the expression of ADAM17 is enhanced. It was expected that the activation of TNF-α, which is a kind of obesity-related cytokine, enhanced colorectal carcinogenesis in obese state.

Academic Significance and Societal Importance of the Research Achievements

肥満関連cytokineの一種であるTNF-αが、大腸がんの発がんに深くかかわっていることは知られていたが、そのメカニズムについては不明な点が多かった。本研究の結果から、肥満環境下ではADAM17の上流に位置するCXCL14の活性が低下することでADAM17の発現が亢進し、結果的にTNF-αの活性化につながるメカニズムが明らかとなった。この結果は肥満関連大腸がんの予防や治療につながる有用な知見であると考えられた。

Research Products

• [Journal Article] Interleukin-13 and Its Signaling Pathway Is Associated With Obesity-Related Colorectal Tumorigenesis (2019)
  • Author(s): Shimpei Matsui, Koji Okabayashi, Masashi Tsuruta, Kohei Shigeta, Ryo Seishima, Takashi Ishida, Takayuki Kondo, Yoshiyuki Suzuki, Hirotoshi Hasegawa, Masayuki Shimoda, Shinya Sugimoto, Toshiro Sato, Yuko Kitagawa
  • Journal Title: Cancer Science Volume: 110 Issue: 7 Pages: 2156-2165
  • DOI: 10.1111/cas.14066
  • Peer Reviewed / Open Access