Firestein, RonBass, AdamKim, So YoungDunn, IanSilver, Serena J.Guney, IsilFreed, EllenLigon, AzraVena, NatalieOgino, ShujiChheda, MilanTamayo, PabloFinn, StephenShrestha, YashaswiBoehm, Jesse S.Jain, Supriya RaniBojarski, EmericMermel, CraigBarretina, JordiChan, JenniferBaselga, JoseTabernero, JosepRoot, David E.Fuchs, CharlesLoda, MassimoShivdasani, RameshMeyerson, MatthewHahn, William2020-05-182008Firestein, Ron, Adam J. Bass, So Young Kim, Ian F. Dunn, Serena J. Silver, Isil Guney, Ellen Freed, et al. 2008. CDK8 Is a Colorectal Cancer Oncogene That Regulates β-Catenin Activity. Nature 455, no. 7212: 547–551.0028-0836http://nrs.harvard.edu/urn-3:HUL.InstRepos:42667705Aberrant activation of the canonical Wnt/β-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated β-catenin activity drives colon tumorigenesis, additional genetic perturbations are required to elaborate fully malignant disease. To identify genes that both modulate β-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. Suppression of CDK8 expression inhibited proliferation in colon cancer cells characterized by high levels of CDK8 and β-catenin hyperactivity. CDK8 kinase activity was necessary for β-catenin driven transformation and expression of several β-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer clinical benefit in β-catenin-driven malignancies.en-USJournal Article2020-05-1810.1038/nature07179