Mechanism of cholangiocarcinogenesis via hepato-cholangiocyte differentiation and conversion by non-classical NF-KB pathway

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17459
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka University
• Principal Investigator: Shiode Yuto 大阪大学, 医学部附属病院, 医員 (10838840)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 胆管癌 / 非古典的NF-kB経路

Outline of Final Research Achievements

Cholangiocarcinoma is the second most common type of primary liver cancer after hepatocellular carcinoma, and is known to have a poor prognosis. Chronic bile duct injury and inflammation, such as primary sclerosing cholangitis and hepatosinusitis, have been known to be risk factors for cholangiocarcinoma for a long time, but the mechanism of the disease has not been clarified. This lack of clarity in the mechanism of cholangiocarcinogenesis is thought to be a hindrance to the development of cholangiocarcinoma therapy. We have identified a novel oncogene for cholangiocarcinoma and created a novel mouse model for cholangiocarcinoma based on this gene. We have also demonstrated that cholangiocarcinoma in these mice occurs through the differentiation and transformation of hepatocytes into cholangiocytes.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

今回我々が発見したTraf3という遺伝子はこれまで胆管癌との関わりは報告されておらず、新規の癌遺伝子である。当遺伝子の発見にはトランスポゾン挿入変異スクリーニング法という、胆管癌に対してはこれまで行われたことのない方法を用いており、このことが新規の癌遺伝子の発見につながったと考えている。また、Traf3を欠損させて作成した胆管癌モデルマウスは短期間で胆管癌を発癌し、今後の治療実験への活用が期待される。肝細胞から胆管への分化転換を阻害することで胆管癌の治療を行うことが可能になれば、今までにないメカニズムでの治療となり、胆管癌の予後改善に寄与することが期待される。