Collapse of intestinal epithelial tissue and its maintenance through TGF-beta family signal

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03456
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: Itoh Susumu 昭和薬科大学, 薬学部, 教授 (70223154)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: TGF-βシグナル / Smad / TMEPAIファミリー / 消化管腫瘍 / β-カテニン

Outline of Final Research Achievements

TMEPAIKO/ApcD716/+ mice showed fewer and smaller intestinal adenoma than ApcD716/+ mice, whereas there were no differences for number and size of adenoma between C18ORF1KO/ApcD716/+ and ApcD716/+ mice.
15-20 weeks after both Smad2 and Smad3 genes were deleted in intestinal eipthelial cells in mice, invasive tumors in small intestines, cecum and/or colon could be found. On the other hand, Smad2 gene alone or Smad3 gene alone was sepcifically knocked out in mouse intestinal eipthelial cells, we could not find any tumors at all.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

TMEPAI遺伝子を欠損させると消化管ポリープ形成が抑制されることを世界で初めて見出すことができた。この結果より、TMEPAIの機能抑制又は発現抑制させる低分子化合物が消化器系がんに対する抗がん剤になる可能性を有することが分かった。
これまでにSmad4やALK3欠損が大腸がんを引き起こすことがわかっていたが、今回世界で初めてTGF-beta/Smadシグナル伝達に関わるSmad2とSmad3遺伝子欠損が消化器系に浸潤がん進展に関与することを突きとめた。