Huang, C. H., Lujambio, A., Zuber, J., Tschaharganeh, D. F., Doran, M. G., Evans, M. J., Kitzing, T., Zhu, N., de Stanchina, E., Sawyers, C. L., Armstrong, S. A., Lewis, J. S., Sherr, C. J., Lowe, S. W. (August 2014) CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. Genes and Development, 28 (16). pp. 1800-1814. ISSN 15495477 (ISSN)
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Abstract
One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are <50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness and the undruggable nature of its main genetic drivers. By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc-driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlight the relevance of transcription elongation in the addiction of cancer cells to MYC. © 2014 Huang et al.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc diseases & disorders > cancer > cancer types > liver cancer |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab |
| Depositing User: | Matt Covey |
| Date: | 15 August 2014 |
| Date Deposited: | 08 Sep 2014 15:37 |
| Last Modified: | 16 Jul 2021 18:53 |
| PMCID: | PMC4197965 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30737 |
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