CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma Journal Article
| Authors: | 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. |
| Article Title: | CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma |
| 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. |
| Keywords: | myc; transcription elongation; oncogene addiction; rnai screen; cdk9 |
| Journal Title: | Genes and Development |
| Volume: | 28 |
| Issue: | 16 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2014-01-01 |
| Start Page: | 1800 |
| End Page: | 1814 |
| Language: | English |
| DOI: | 10.1101/gad.244368.114 |
| PROVIDER: | scopus |
| PUBMED: | 25128497 |
| PMCID: | PMC4197965 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2014 -- CODEN: GEDEE -- Source: Scopus |
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