STANDARD_NAME FIRESTEIN_CTNNB1_PATHWAY_AND_PROLIFERATION SYSTEMATIC_NAME M16807 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/FIRESTEIN_CTNNB1_PATHWAY_AND_PROLIFERATION NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes required for both proliferation and CTNNB1 [GeneID=1499] activity in DLD-1 cell (colon cancer with APC [GeneID=324] deletions). DESCRIPTION_FULL 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. PMID 18794900 GEOID AUTHORS Firestein R,Bass AJ,Kim SY,Dunn IF,Silver SJ,Guney I,Freed E,Ligon AH,Vena N,Ogino S,Chheda MG,Tamayo P,Finn S,Shrestha Y,Boehm JS,Jain S,Bojarski E,Mermel C,Barretina J,Chan JA,Baselga J,Tabernero J,Root DE,Fuchs CS,Loda M,Shivdasani RA,Meyerson M,Hahn WC CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Fig. 1D FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS CDK8,CSNK1E,CSNK1G3,DKC1,MAP3K14,MLLT7,PLK4,TAOK1,ZAK GENE_SYMBOLS CDK8,CSNK1E,CSNK1G3,DKC1,MAP3K14,FOXO4,PLK4,TAOK1,MAP3K20 FOUNDER_NAMES