| First Author | Topham C | Year | 2015 |
| Journal | Cancer Cell | Volume | 28 |
| Issue | 1 | Pages | 129-40 |
| PubMed ID | 26175417 | Mgi Jnum | J:222993 |
| Mgi Id | MGI:5646310 | Doi | 10.1016/j.ccell.2015.06.001 |
| Citation | Topham C, et al. (2015) MYC Is a Major Determinant of Mitotic Cell Fate. Cancer Cell 28(1):129-40 |
| abstractText | 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. |
