Elucidation of the mechanism of metastasis using CRISPR knockout library in colorectal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16772
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Osaka University
• Principal Investigator: Ishikawa Satoshi 大阪大学, 医学部附属病院, 医員 (90804021)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 上皮間葉転換 / 大腸癌 / バイオインフォマティクス

Outline of Final Research Achievements

As a comprehensive analysis of the genes involved in epithelial-mesenchymal transition (EMT), we initially attempted to screen the genes using a CRISPR knockout library. However, this system did not work well due to the variability in response to TGFβ among cell lines. Therefore, we isolated cancer epithelium and stroma and analyzed them with gene expression data from public databases to comprehensively identify EMT-inducing genes. One of these genes, ARC, was involved in EMT of colorectal cancer cells in vitro, and its expression was correlated with the recurrence of colorectal cancer in clinical samples. Further analysis of the candidate genes is expected to contribute to understanding the complex EMT program and the development of therapeutic agents targeting them.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

上皮間葉転換は様々な癌種の転移プロセスに中心的な役割を果たすことが知られているが、関連する分子の全体像は明らかとなっていない。本研究では大腸癌細胞の上皮間葉転換に関連する遺伝子をバイオインフォマティクスの手法を用いて網羅的に同定することに成功した。個々の遺伝子についてはさらなる研究が必要であるが、上皮間葉転換の全体像を理解し、それを標的とする治療法開発につながる可能性があるという点で学術的意義は大きいと考える。