Human Gene Set: FEVR_CTNNB1_TARGETS_DN


Standard name FEVR_CTNNB1_TARGETS_DN
Systematic name M2343
Brief description Genes down-regulated in intestinal crypt cells upon deletion of CTNNB1 [GeneID=1499].
Full description or abstract The Wnt signaling pathway is deregulated in over 90% of human colorectal cancers. beta-Catenin, the central signal transducer of the Wnt pathway, can directly modulate gene expression by interacting with transcription factors of the TCF/LEF family. In the present study we investigate the role of Wnt signaling in the homeostasis of intestinal epithelium by using tissue-specific, inducible beta-catenin gene ablation in adult mice. Block of Wnt/beta-catenin signaling resulted in rapid loss of transient-amplifying cells and crypt structures. Importantly, intestinal stem cells were induced to terminally differentiate upon deletion of beta-catenin, resulting in a complete block of intestinal homeostasis and fatal loss of intestinal function. Transcriptional profiling of mutant crypt mRNA isolated by laser capture microdissection confirmed those observations and allowed us to identify genes potentially responsible for the functional preservation of intestinal stem cells. Our data demonstrate an essential requirement of Wnt/beta-catenin signaling for the maintenance of the intestinal epithelium in the adult organism. This challenges attempts to target aberrant Wnt signaling as a new therapeutic strategy to treat colorectal cancer.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17785439   Authors: Fevr T,Robine S,Louvard D,Huelsken J
Exact source Table 2S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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