Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. Genes Dev 2014 Aug 15;28(16):1800-14

Date

08/17/2014

Pubmed ID

25128497

Pubmed Central ID

PMC4197965

DOI

10.1101/gad.244368.114

Scopus ID

2-s2.0-84906074303 (requires institutional sign-in at Scopus site)   155 Citations

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.

Author List

Huang CH, Lujambio A, Zuber J, Tschaharganeh DF, Doran MG, Evans MJ, Kitzing T, Zhu N, de Stanchina E, Sawyers CL, Armstrong SA, Lewis JS, Sherr CJ, Lowe SW



MESH terms used to index this publication - Major topics in bold

Animals
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase 9
Female
Gene Expression
Gene Library
Hep G2 Cells
Humans
Liver Neoplasms
Mice
Positive Transcriptional Elongation Factor B
Proto-Oncogene Proteins c-myc
RNA Interference
RNA, Small Interfering
Transcription Elongation, Genetic