Cell-cycle position of single MYC-driven cancer cells dictates their susceptibility to a chemotherapeutic drug
Summary: While many tumors initially respond to chemotherapy, regrowth of surviving cells compromises treatment efficacy in the long term. The cell-biological basis of this regrowth is not understood. Here, we characterize the response of individual, patient-derived neuroblastoma cells driven by th...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
23 August 2017
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| In: |
Cell systems
Year: 2017, Volume: 5, Issue: 3 |
| ISSN: | 2405-4720 |
| DOI: | 10.1016/j.cels.2017.07.005 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.cels.2017.07.005 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2405471217303319 
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| Author Notes: | Tatsiana Ryl, Erika E. Kuchen, Emma Bell, Chunxuan Shao, Andrés F. Flórez, Gregor Mönke, Sina Gogolin, Mona Friedrich, Florian Lamprecht, Frank Westermann, Thomas Höfer |
| Summary: | Summary: While many tumors initially respond to chemotherapy, regrowth of surviving cells compromises treatment efficacy in the long term. The cell-biological basis of this regrowth is not understood. Here, we characterize the response of individual, patient-derived neuroblastoma cells driven by the prominent oncogene MYC to the first-line chemotherapy, doxorubicin. Combining live-cell imaging, cell-cycle-resolved transcriptomics, and mathematical modeling, we demonstrate that a cell's treatment response is dictated by its expression level of MYC and its cell-cycle position prior to treatment. All low-MYC cells enter therapy-induced senescence. High-MYC cells, by contrast, disable their cell-cycle checkpoints, forcing renewed proliferation despite treatment-induced DNA damage. After treatment, the viability of high-MYC cells depends on their cell-cycle position during treatment: newborn cells promptly halt in G1 phase, repair DNA damage, and form re-growing clones; all other cells show protracted DNA repair and ultimately die. These findings demonstrate that fast-proliferating tumor cells may resist cytotoxic treatment non-genetically, by arresting within a favorable window of the cell cycle. |
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| Item Description: | Gesehen am 28.05.2018 Available online 23 August 2017 |
| Physical Description: | Online Resource |
| ISSN: | 2405-4720 |
| DOI: | 10.1016/j.cels.2017.07.005 |