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 |
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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 > School 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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