CDK8 is a colorectal cancer oncogene that regulates β-catenin activity

Ron Firestein, Adam J. Bass, So Young Kim, Ian F. Dunn, Serena J. Silver, Isil Guney, Ellen Freed, Azra H. Ligon, Natalie Vena, Shuji Ogino, Milan G. Chheda, Pablo Tamayo, Stephen Finn, Yashaswi Shrestha, Jesse S. Boehm, Supriya Jain, Emeric Bojarski, Craig Mermel, Jordi Barretina, Jennifer A. Chan, Jose Baselga, Josep Tabernero, David E. Root, Charles S. Fuchs, Massimo Loda, Ramesh A. Shivdasani, Matthew Meyerson and William C. Hahn ()
Additional contact information
Ron Firestein: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Adam J. Bass: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
So Young Kim: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Ian F. Dunn: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Serena J. Silver: Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Isil Guney: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Ellen Freed: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Azra H. Ligon: Department of Pathology,
Natalie Vena: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Shuji Ogino: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Milan G. Chheda: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Pablo Tamayo: Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Stephen Finn: Department of Pathology,
Yashaswi Shrestha: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Jesse S. Boehm: Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Supriya Jain: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Emeric Bojarski: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Craig Mermel: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Jordi Barretina: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Jennifer A. Chan: Department of Pathology,
Jose Baselga: Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain
Josep Tabernero: Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain
David E. Root: Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Charles S. Fuchs: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Massimo Loda: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Ramesh A. Shivdasani: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Matthew Meyerson: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
William C. Hahn: Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA

Nature, 2008, vol. 455, issue 7212, 547-551

Abstract: CCK8 and WNT signalling linked in colorectal cancer The WNT/ β-catenin signalling pathway, which normally plays a pivotal part in development, is deregulated in almost all colorectal cancers. Retinoblastoma tumour suppressor protein (pRB) is a cell-cycle regulator that is mutated in many different types of cancer. Two papers in this issue show that signalling through the WNT pathway and that mediated by pRB are highly interconnected, and that a common denominator of their deregulation is colorectal cancer. Firestein et al. combined RNAi screening for genes required for colon cancer cell proliferation with genomic data from human colon cancer to identifty CDK8 as a novel human oncogene. CDK8, a general transcriptional regulator, functions in part by enhancing the activity of the Wnt signalling pathway. Morris et al. report that E2F1, a transcription factor that is a target of pRB, is a potent and specific inhibitor of β-catenin, and that its activity is negatively regulated by CDK8. They point out that the interaction between E2F1 and β-catenin explains the long-standing paradox that pRB, an important tumour suppressor in most other contexts, is preserved in colorectal carcinomas. In an accompanying News & Views, René Bernards considers how the crosstalk between E2F and β-catenin signalling can lead to colorectal cancer.

Date: 2008
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/nature07179 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:455:y:2008:i:7212:d:10.1038_nature07179

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature07179

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().