Impairment of DYRK2 augments stem-like traits by promoting KLF4 expression in breast cancer.
Oncogene
; 36(13): 1862-1872, 2017 03 30.
Article
en En
| MEDLINE
| ID: mdl-27721402
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
/
Proteínas Tirosina Quinasas
/
Neoplasias de la Mama
/
Regulación Neoplásica de la Expresión Génica
/
Proteínas Serina-Treonina Quinasas
/
Factores de Transcripción de Tipo Kruppel
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón