| Project/Area Number |
18K16267
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | The University of Tokyo (2022)
Jikei University School of Medicine (2018-2021) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | DYRK2 / 乳癌 / 腫瘍増殖 / CDK14 |
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| Outline of Final Research Achievements |
Tumor progression is the main cause of death in patients with breast cancer. Accumulating evidence suggests that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation and apoptosis. However, little is known about the mechanisms of transcriptional regulation by DYRK2 in cancer progression, particularly with respect to cancer proliferation and invasion.
Here, using a comprehensive expression profiling approach, we show that cyclin-dependent kinase 14 (CDK14) is a target of DYRK2. We further identified androgen receptor (AR) as a candidate of DYRK2-dependent transcription factors regulating CDK14.
Our findings demonstrate that reduced DYRK2 expression in breast cancer promotes tumor cell proliferation and invasion by modulating CDK14 expression via AR, and inhibits the growth by treatment with AR inhibitor, MDV3100.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、乳癌におけるDYRK2によるCDK14の発現制御機構を解明し、更にDYRK2の発現が低い乳癌に対して、治療効果が期待出来る化合物を同定した。
臨床検体を用いた病理解析も併せて行ったことで、基礎研究での成果を臨床での「DYRK2の発現の低い、すなわち悪性度の高い乳癌に特異的な治療法の確立」へと繋げる架け橋のような知見を見出すことが出来たと考える。
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