MYC is a major determinant of mitotic cell fate

Topham, C. et al. (2015) MYC is a major determinant of mitotic cell fate. Cancer Cell, 28(1), pp. 129-140. (doi:10.1016/j.ccell.2015.06.001) (PMID:26175417) (PMCID:PMC4518499)

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Abstract

Taxol and other antimitotic agents are frontline chemotherapy agents but the mechanisms responsible for patient benefit remain unclear. Following a genome-wide siRNA screen, we identified the oncogenic transcription factor Myc as a taxol sensitizer. Using time-lapse imaging to correlate mitotic behavior with cell fate, we show that Myc sensitizes cells to mitotic blockers and agents that accelerate mitotic progression. Myc achieves this by upregulating a cluster of redundant pro-apoptotic BH3-only proteins and suppressing pro-survival Bcl-xL. Gene expression analysis of breast cancers indicates that taxane responses correlate positively with Myc and negatively with Bcl-xL. Accordingly, pharmacological inhibition of Bcl-xL restores apoptosis in Myc-deficient cells. These results open up opportunities for biomarkers and combination therapies that could enhance traditional and second-generation antimitotic agents.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ridgway, Dr Rachel and Sansom, Professor Owen
Authors: Topham, C., Tighe, A., Ly, P., Bennett, A., Sloss, O., Nelson, L., Ridgway, R.A., Huels, D., Littler, S., Schandl, C., Sun, Y., Bechi, B., Procter, D.J., Sansom, O.J., Cleveland, D.W., and Taylor, S.S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Cell
Publisher:Elsevier
ISSN:1535-6108
ISSN (Online):1878-3686
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Cancer Cell 28(1):129-140
Publisher Policy:Reproduced under a Creative Commons License

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