Human Gene Set: FIRESTEIN_CTNNB1_PATHWAY


Standard name FIRESTEIN_CTNNB1_PATHWAY
Systematic name M1489
Brief description Genes required for CTNNB1 [GeneID=1499] activity in DLD-1 cell (colon cancer with APC [GeneID=324] deletions), based on shRNA screen.
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18794900   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
Exact source Table 1S: Z score <= -2
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 Human_RefSeq
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Version history 3.0: First introduced

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