Journal
ONCOGENE
Volume 36, Issue 13, Pages 1862-1872Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2016.349
Keywords
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Funding
- JSPS KAKENHI [26290041, 26861056]
- Takeda Science Foundation
- Vehicle Racing Commemorative Foundation
- Research Grant of the Princess Takamatsu Cancer Research Fund
- Grants-in-Aid for Scientific Research [26290041, 26861056] Funding Source: KAKEN
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Whereas accumulating studies have supported the cancer stem cell theory, a specific therapy targeting a cancer stem cell subpopulation has not been established. Here, we show that dual-specificity tyrosine phosphorylation-kinase 2 (DYRK2) is a novel negative regulator for formation of breast cancer stem cells. Downregulation of DYRK2 promotes cancer stem-like traits in vitro, tumourigenesis in vivo and the proportion of the cancer stem cell population in human breast cancer tissues. We found that Krupple-like factor 4 (KLF4) serves as a key mediator of DYRK2's control over the cancer stem phenotype. Reduced DYRK2 expression increases KLF4 expression, which induces cancer stem-like properties. We identified androgen receptor (AR) as a transcription factor binding to the KLF4 promoter region; this process is dependent on DYRK2 kinase activity. Our findings delineate a mechanism of cancer stem cell regulation by the DYRK2-AR-KLF4 axis in breast cancer. Targeting of this pathway may be a promising strategy against breast cancer stem cells.
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