You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Depletion of kinesin motor KIF20A to target cell fate control suppresses medulloblastoma tumour growth
Contributor:
Qiu, Runxiang;
Wu, Jun;
Gudenas, Brian;
Northcott, Paul A.;
Wechsler-Reya, Robert J.;
Lu, Qiang
imprint:
Springer Science and Business Media LLC, 2021
Published in:Communications Biology
Language:
English
DOI:
10.1038/s42003-021-02075-4
ISSN:
2399-3642
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>During mammalian brain development, neural progenitor cells proliferate extensively but can ensure the production of correct numbers of various types of mature cells by balancing symmetric proliferative versus asymmetric differentiative cell divisions. This process of cell fate determination may be harnessed for developing cancer therapy. Here, we test this idea by targeting KIF20A, a mitotic kinesin crucial for the control of cell division modes, in a genetic model of medulloblastoma (MB) and human MB cells. Inducible <jats:italic>Kif20a</jats:italic> knockout in both normal and MB-initiating granule neuron progenitors (GNPs) causes early cell cycle exit and precocious neuronal differentiation without causing cytokinesis failure and suppresses the development of Sonic Hedgehog (SHH)-activated MB. Inducible KIF20A knockdown in human MB cells inhibits proliferation both in cultures and in growing tumors. Our results indicate that targeting the fate specification process of nascent daughter cells presents a novel avenue for developing anti-proliferation treatment for malignant brain tumors.</jats:p>