RGD Reference Report - DDB2 Is a Novel Regulator of Wnt Signaling in Colon Cancer. - Rat Genome Database

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DDB2 Is a Novel Regulator of Wnt Signaling in Colon Cancer.

Authors: Huang, Shuo  Fantini, Damiano  Merrill, Bradley J  Bagchi, Srilata  Guzman, Grace  Raychaudhuri, Pradip 
Citation: Huang S, etal., Cancer Res. 2017 Dec 1;77(23):6562-6575. doi: 10.1158/0008-5472.CAN-17-1570. Epub 2017 Oct 11.
RGD ID: 151361223
Pubmed: PMID:29021137   (View Abstract at PubMed)
PMCID: PMC5712251   (View Article at PubMed Central)
DOI: DOI:10.1158/0008-5472.CAN-17-1570   (Journal Full-text)

Deregulation of the Wnt/β-catenin signaling pathway drives the development of colorectal cancer, but understanding of this pathway remains incomplete. Here, we report that the damage-specific DNA-binding protein DDB2 is critical for β-catenin-mediated activation of RNF43, which restricts Wnt signaling by removing Wnt receptors from the cell surface. Reduced expression of DDB2 and RNF43 was observed in human hyperplastic colonic foci. DDB2 recruited EZH2 and β-catenin at an upstream site in the Rnf43 gene, enabling functional interaction with distant TCF4/β-catenin-binding sites in the intron of Rnf43 This novel activity of DDB2 was required for RNF43 function as a negative feedback regulator of Wnt signaling. Mice genetically deficient in DDB2 exhibited increased susceptibility to colon tumor development in a manner associated with higher abundance of the Wnt receptor-expressing cells and greater activation of the downstream Wnt pathway. Our results identify DDB2 as both a partner and regulator of Wnt signaling, with an important role in suppressing colon cancer development. Cancer Res; 77(23); 6562-75. ©2017 AACR.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RNF43Humancolorectal cancer  ISORnf43 (Mus musculus)protein:decreased expression:colorectum (mouse)RGD 
Rnf43Ratcolorectal cancer  ISORnf43 (Mus musculus)protein:decreased expression:colorectum (mouse)RGD 
Rnf43Mousecolorectal cancer  IEP protein:decreased expression:colorectum (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rnf43  (ring finger protein 43)

Genes (Mus musculus)
Rnf43  (ring finger protein 43)

Genes (Homo sapiens)
RNF43  (ring finger protein 43)


Additional Information