Molecular mechanism of tumor metastasis driven by cancer stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03584
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• 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): 2017-04-01 – 2020-03-31
• Keywords: 癌 / 幹細胞 / 転移

Outline of Final Research Achievements

Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of EMT is the key step for metastasis of cancer cells. We have recently demonstrated in breast cancer and ovarian serous adenocarcinoma that DYRK2 controls EMT. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We demonstrated that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by an ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases 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、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腫瘍転移機構に発展させた。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を抑制できることを示した。従ってDYRK2が転移抑制分子として臨床応用への展開が期待される。