Mechanisms of initiation and progression of thymic epithelial tumor

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16221
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Keio University
• Principal Investigator: Ueda Fumihito 慶應義塾大学, 薬学部(芝共立), 助教 (20806129)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: Hippo経路 / 胸腺上皮細胞 / 胸腺がん

Outline of Final Research Achievements

Since thymic epithelial tumors frequently accompany autoimmune diseases such as myasthenia gravis, understanding the mechanism of their onset and progression is important either oncologically and immunologically, but they are too rare to be analyzed enough. Using mice lacking the Hippo pathway-constituting gene specific to the thymic epithelium, we elucidate the onset and progression mechanism of thymic epithelial tumors and verify the possibility of treatment targeting the Hippo pathway.
As a result of analysis using various genetically modified mice, it was shown that disruption of the Hippo pathway activates YAP, which is a downstream effector molecule of Hippo pathway, leading to the development of thymic cancer, and the possibility of effectiveness against thymic cancer by targeting YAP.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究は、胸腺上皮性腫瘍の中でも特に稀な症例である胸腺がんに関して新たな知見を与えた。単一の遺伝子欠損で非常に早期に胸腺がんを発症する本モデルマウスは今後の胸腺がん研究において有用であるだけでなく、胸腺がんに対する治療薬としてYAPを標的とした薬剤が有用である可能性を提示できたことから、社会的にも本研究成果が与える影響は大きい。