MYC is a major determinant of mitotic cell fate

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: 28 Aug 2021 17:54
URI: http://usir.salford.ac.uk/id/eprint/37651

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