Topham, C 
ORCID: https://orcid.org/0000-0001-9974-2407, Tighe, A, Ly, P, Bennett, A, Sloss, O, Nelson, L, Ridgway, RA, Huels, D, Littler, S, Schandl, C, Sun, Y, Bechi, B, Procter, DJ, Sansom, OJ, Cleveland, DW and Taylor, SS
2015,
'MYC is a major determinant of mitotic cell fate'
, Cancer Cell, 28 (1)
, pp. 129-140.
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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: | Article |
|---|---|
| Schools: | Schools > School of Environment and Life Sciences > Biomedical Research Centre |
| Journal or Publication Title: | Cancer Cell |
| Publisher: | Cell Press (Elsevier) |
| ISSN: | 1535-6108 |
| Related URLs: | |
| Funders: | Cancer Research UK, Medical Research Council (MRC), Wellcome Trust |
| Depositing User: | CH Topham |
| Date Deposited: | 22 Dec 2015 15:19 |
| Last Modified: | 15 Feb 2022 20:08 |
| URI: | https://usir.salford.ac.uk/id/eprint/37651 |
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