Elucidation of the carcinogenic mechanisms of bile duct cancer focusing on genetic mutations based on the site of occurrence.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15528
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyoto University (2023); Kobe University (2022)
• Principal Investigator: Nishikawa Yoshihiro 京都大学, 医学研究科, 特定助教 (80802785)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 胆嚢癌 / 胆道癌 / ELF3

Outline of Final Research Achievements

We aimed to elucidate the role of ELF3 in gallbladder tumorigenesis using human samples, public data, mouse models, and organoids. It was revealed that ELF3 functions as a tumor suppressor, likely through the regulation of EREG and its downstream AKT/PI3K/mTORC1 pathway. Loss of ELF3 ultimately led to enhanced EMT, promoting tumor formation. Since the loss of ELF3 increases dependence on the AKT/PI3K/mTORC1 pathway, the inhibition of mTORC1 suppressed tumors, suggesting that mTORC1 could be a potential therapeutic target for ELF3-mutant gallbladder cancer.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

胆道癌は予後不良な難治癌の一つであり、予後改善・新規治療薬の開発には、その病態解明が必須である。ELF3は胆嚢癌において21%に変異を認めるという報告があり、がん抑制性の役割を担っていると考えられていたものの、詳細は不明であった。本研究でその病態形成の詳細を明らかにすることが出来た。実際の新規治療法開発には更なる検討が必要と考えられる。