Elucidation for molecular mechanism of cancer stem cells by the live-imaging technology

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19484
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• 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): 2018-06-29 – 2021-03-31
• Keywords: がん幹細胞 / 細胞分裂

Outline of Final Research Achievements

We found that downregulation of DYRK2 promotes cancer stem-like traits in vitro, tumourigenesis in vivo, and the proportion of the cancer stem cell population. KLF4 serves as a key mediator of DYRK2’s control over the cancer stem phenotype. Our findings delineate a mechanism of cancer stem cell regulation by the DYRK2-AR-KLF4 axis. Targeting of this pathway may be a promising strategy against cancer stem cells.
We also found that silencing of DYRK2 increased CDK14. Reduced DYRK2 expression increases CDK14 expression, which promotes cancer cell proliferation and invasion. CDK14 and DYRK2 expression inversely correlated. We identified androgen receptor (AR) as a DYRK2-dependent transcription factor regulating CDK14. Our findings suggest a mechanism by which a DYRK2-AR-CDK14 interaction regulates cell proliferation and invasion. Targeting of this pathway may be a promising therapeutic strategy for treating cancer.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

がん幹細胞はがん細胞の中で幹細胞様の性質をもつ細胞集団として知られており、自己複製能、高い治療抵抗性をもつ。これら幹細胞様の性質は、浸潤や転移、再発などの原因となると考えられている。がん幹細胞は腫瘍内に極少数の割合で存在していると考えられているが、がん幹細胞に制御に関わる因子や細胞内シグナル伝達経路については不明な点が多い。本研究からPim-1、DYRK２、CA13などこれまで知られていなかったがん幹細胞制御分子の同定に成功しており、これらの分子をターゲットとした治療法開発の端緒となることが期待される。