Identification of a novel cancer stem cell-related gene in cholangiocarcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15495
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: Fujimori Haruna 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん幹細胞研究部, 研究員 (80882935)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: PDX / FAXC / ANXA2

Outline of Final Research Achievements

Tumor heterogeneity is a well-known characteristic of cancer. Some cancer cells that survive after therapy are highly tumorigenic and contribute to metastasis and recurrence. To develop a therapeutic strategy targeting the highly tumorigenic cancer cells, we screened for a novel gene associated with tumorigenicity in cholangiocarcinoma (CCA). As a result, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in immunodeficient mice. In addition, FAXC bound to the tumor-promoting genes annexin A2 (ANXA2) and c-SRC at the mitochondria and enhanced SRC-dependent ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with hypoxia-related genes. Taken together, these findings further our understanding of CCA tumorigenesis.

Free Research Field

がん生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

FAXCはこれまで一切報告のなかった機能未知遺伝子で、癌との関連報告も初めてである。そのため、今回見出した現象はすべてがん生物学的に新しく、また新規の治療標的として期待される。