CDK8 is a colorectal cancer oncogene that regulates β-catenin activity Academic Article uri icon

Overview

MeSH Major

  • Colorectal Neoplasms
  • Cyclin-Dependent Kinases
  • Gene Expression Regulation, Neoplastic
  • Oncogenes
  • beta Catenin

abstract

  • Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To identify genes that both modulate beta-catenin activity and are essential for colon cancer cell proliferation, we conducted two loss-of-function screens in human colon cancer cells and compared genes identified in these screens with an analysis of copy number alterations in colon cancer specimens. One of these genes, CDK8, which encodes a member of the mediator complex, is located at 13q12.13, a region of recurrent copy number gain in a substantial fraction of colon cancers. Here we show that the suppression of CDK8 expression inhibits proliferation in colon cancer cells characterized by high levels of CDK8 and beta-catenin hyperactivity. CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer a clinical benefit in beta-catenin-driven malignancies.

publication date

  • September 25, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2587138

Digital Object Identifier (DOI)

  • 10.1038/nature07179

PubMed ID

  • 18794900

Additional Document Info

start page

  • 547

end page

  • 51

volume

  • 455

number

  • 7212