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Article

DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

1
Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
2
School of Chemistry, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia
3
QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia
*
Authors to whom correspondence should be addressed.
Academic Editor: Guillermo Gomez
Int. J. Mol. Sci. 2021, 22(8), 4011; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084011
Received: 19 March 2021 / Revised: 7 April 2021 / Accepted: 7 April 2021 / Published: 13 April 2021
Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance. View Full-Text
Keywords: glioblastoma; cancer stem cells; DYRK1A; CDK5; SOX2; bone morphogenetic protein 4 (BMP4) glioblastoma; cancer stem cells; DYRK1A; CDK5; SOX2; bone morphogenetic protein 4 (BMP4)
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MDPI and ACS Style

Chen, B.; McCuaig-Walton, D.; Tan, S.; Montgomery, A.P.; Day, B.W.; Kassiou, M.; Munoz, L.; Recasens, A. DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells. Int. J. Mol. Sci. 2021, 22, 4011. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084011

AMA Style

Chen B, McCuaig-Walton D, Tan S, Montgomery AP, Day BW, Kassiou M, Munoz L, Recasens A. DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells. International Journal of Molecular Sciences. 2021; 22(8):4011. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084011

Chicago/Turabian Style

Chen, Brianna, Dylan McCuaig-Walton, Sean Tan, Andrew P. Montgomery, Bryan W. Day, Michael Kassiou, Lenka Munoz, and Ariadna Recasens. 2021. "DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells" International Journal of Molecular Sciences 22, no. 8: 4011. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084011

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