Clarification of Cdh1 mediated inflammatory carcinogenesis mechanism revealed by spatial gene expression analysis and development of novel preventive strategies.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kumamoto University
• Principal Investigator: Naoe Hideaki 熊本大学, 大学院生命科学研究部(医), 准教授 (30599246)
• Co-Investigator(Kenkyū-buntansha): 古田 陽輝 熊本大学, 病院, 特任助教 (00869513) ; 渡邊 丈久 熊本大学, 大学院生命科学研究部(医), 助教 (20634843)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 炎症性発癌

Outline of Final Research Achievements

①Choline-deficient - high-fat diet was fed to control and Cdh1-active mice to induce hepatocellular carcinooma; the number and size of tumours formed in the liver of these mice were measured at 24 and 56 weeks. The results showed no significant differences between the two groups of mice.
②Tumours were formed in the colon of control and Cdh1-active mice induced by the AOM-DSS model. RNA was extracted from these tumours and RNA seq analysis showed no significant deferences between two groups. Therefore, RNA extracted from the backgound inflammatory mucosa surrounding the tumors was analysed and found to be significantly altered in the expression of Wnt6, Wnt10a, Axin, LEF and others between the two groups.

Free Research Field

消化器癌

Academic Significance and Societal Importance of the Research Achievements

Cdh1活性型マウスの大腸炎症粘膜において有意に発現が亢進していたRNAはWnt6、Wnt10a、Axin、LEF等であった。これらは、代表的な発癌経路である古典的Wnt-βカテニン経路を構成する遺伝子群である。Cdh1が、Wnt-βカテニン経路と強く関連していたことから、Cdh1が大腸の炎症性発癌の過程で未知の機能を有しているのではないかと考えられる。Cdh1をターゲットにすることで、大腸炎症性発癌の予防あるいは治療法へとつながる可能性が示唆される。