CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

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)

[img]
Preview
PDF (Paper)
Lowe Genes & Development 2014.pdf - Published Version

Download (2079Kb) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/25128497
DOI: 10.1101/gad.244368.114

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: 25 Oct 2018 16:14
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30737

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving