Elucidation for molecular mechanism of carcinogenesis driven by cancer stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03519
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Yoshida Kiyotsugu 東京慈恵会医科大学, 医学部, 教授 (70345312)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 癌 / 幹細胞

Outline of Final Research Achievements

Colorectal cancer is the most common gastrointestinal tumors. DYRK2 functions as a tumor suppressor in colorectal cancer by regulating cell survival, proliferation, and apoptosis induction. In addition, DYRK2 expression is decreased in tumor tissues compared to nontumor tissues in colorectal cancer, indicating a correlation with clinical prognosis. In this regard, we devised a novel therapeutic strategy to overexpress DYRK2 in tumors by adenovirus-mediated gene transfer. Overexpression of DYRK2 in colon cancer cell lines by adenovirus inhibited cell proliferation and induced apoptosis in vitro. In mouse subcutaneous xenograft and liver metastasis models, enforced expression of DYRK2 by direct or intravenous injection of adenovirus to the tumor significantly inhibited tumor growth. These findings show that adenovirus-based overexpression of DYRK2 could be a novel gene therapy for liver metastasis of colorectal cancer.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

癌幹細胞は高い腫瘍形成能を持ち、発癌のみならず、転移や再発の原因になると考えられている。一方で多くの抗癌剤に耐性を示すことから、癌幹細胞を標的とした治療法の開発が切望されている。我々はすでにDYRK2が癌幹細胞の発生・維持制御分子であることを明らかにしており、本研究ではこの知見を発癌制御機構に発展させた。研究成果として大腸癌の肝転移モデルマウスを用いてDYRK2を発現させることで、酵素活性依存的に転移癌の増殖を抑制できることを示した。従ってDYRK2が発癌抑制分子として臨床応用への展開が期待される。