Gene Set: SANSOM_WNT_PATHWAY_REQUIRE_MYC

Standard name SANSOM_WNT_PATHWAY_REQUIRE_MYC
Systematic name M1758
Brief description Wnt target genes up-regulated after Cre-lox knockout of APC [GeneID=324] in the small intestine that require functional MYC [GeneID=4609].
Full description or abstract The APC gene encodes the adenomatous polyposis coli tumour suppressor protein, germline mutation of which characterizes familial adenomatous polyposis (FAP), an autosomal intestinal cancer syndrome. Inactivation of APC is also recognized as the key early event in the development of sporadic colorectal cancers, and its loss results in constitutive activity of the beta-catenin-Tcf4 transcription complex. The proto-oncogene c-MYC has been identified as a target of the Wnt pathway in colorectal cancer cells in vitro, in normal crypts in vivo and in intestinal epithelial cells acutely transformed on in vivo deletion of the APC gene; however, the significance of this is unclear. Therefore, to elucidate the role Myc has in the intestine after Apc loss, we have simultaneously deleted both Apc and Myc in the adult murine small intestine. Here we show that loss of Myc rescued the phenotypes of perturbed differentiation, migration, proliferation and apoptosis, which occur on deletion of Apc. Remarkably, this rescue occurred in the presence of high levels of nuclear beta-catenin. Array analysis revealed that Myc is required for the majority of Wnt target gene activation following Apc loss. These data establish Myc as the critical mediator of the early stages of neoplasia following Apc loss.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17377531   Authors: Sansom OJ,Meniel VS,Muncan V,Phesse TJ,Wilkins JA,Reed KR,Vass JK,Athineos D,Clevers H,Clarke AR
Exact source Table 4S
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(show 58 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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