Role of gastric microbiota on the development of gastric cacner stem-cells in H. pylori-infected gastric mucosa
| Project/Area Number |
19K07068
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
|
|---|
| Research Institution | Tokai University (2021)
Keio University (2019-2020) |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | がん幹細胞 / ピロリ菌 / 胃内細菌叢 / 胃オルガノイド / 癌幹細胞 / CD44v9 / ステムセル / 胃がん / 胃内共生細菌 / 細菌叢 / 胃癌 |
|---|
| Outline of Research at the Start |
CD44v9陽性癌幹細胞は胃癌発症要因の責任細胞となるが、どの様に発生するか理解されていない。CAPZA1の過剰発現細胞はオートファジー不全となり、H. pyloriの癌蛋白質CagAを蓄積させる。CAPZA1発現はヒストンのアセチル化制御を受け、「消化管内短鎖脂肪酸は、CAPZA1発現を亢進させ、そこへのH. pylori感染により、CAPZA1過剰発現細胞はCD44v9陽性癌幹細胞へ脱分化される」と仮説できる。本研究課題では、H. pylori感染胃粘膜で消化管内細菌がSCFAsを介してCAPZA1発現を惹起しCD44v9陽性癌幹細胞の発生に寄与しているかを明らかにする。
|
| Outline of Final Research Achievements |
We identified two short-chain fatty acids (SCFAs)-producing bacteria that cause CAPZA1-overexpressing cells, which are precursors to CD44v9-positive cancer stem cells. It was clarified that CD44v9-positive cancer stem cells are produced by H. pylori infection in the presence of SCFAs produced by these bacteria. In H. pylori-infected mice given drinking water containig propionic acid or butyric acid, CD44v9-positive cells were generated through overexpression of CAPZA1 in gastric mucosal epithelial cells. Our results indicate that HDAC inhibitory activity of SCFAs deregulates CAPZA1 expression, and H. pylori infection under specific SCFAs-producing bacteria enhancces the development of CD44v9-positive cancer stem cells.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、がん幹細胞の発生過程に共生細菌が関与するというこれまでに類のない全く新しいがん幹細胞発生モデルを分子生物学的に提唱でき、学術的な発展が大いに期待できる。また、本研究成果を基盤に胃内共生細菌叢への介入による胃がんの発症・再発リスク評価系や胃発がん予防・治療法の開発も期待され、今日のがん予防・治療法に革新的な変化をもたらし、臨床医学的にも期待値の大きい基礎エビデンスの提唱が実現される。
|
Report
(4 results)
Research Products
(22 results)
-
-
[Journal Article] Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 12021
Author(s)
Yasuaki Kabe, Ikko Koike, Tatsuya Yamamoto, Miwa Hirai, Ayaka Kanai, Ryogo Furuhata, Hitoshi Tsugawa, Erisa Harada, Kenji Sugase, Kazue Hanadate, Nobuji Yoshikawa, Hiroaki Hayashi, Masanori Noda, Susumu Uchiyama, Hiroki Yamazaki, Hirotoshi Tanaka, Takuya Kobayashi, Hiroshi Handa, Makoto Suematsu.
-
Journal Title
Cancers (Basel)
Volume: 13
Issue: 13
Pages: 3265-3265
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
