Document Detail


CDX2 is an amplified lineage-survival oncogene in colorectal cancer.
MedLine Citation:
PMID:  23112155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mutational activation of oncogenes drives cancer development and progression. Classic oncogenes, such as MYC and RAS, are active across many different cancer types. In contrast, "lineage-survival" oncogenes represent a distinct and emerging class typically comprising transcriptional regulators of a specific cell lineage that, when deregulated, support the proliferation and survival of cancers derived from that lineage. Here, in a large collection of colorectal cancer cell lines and tumors, we identify recurrent amplification of chromosome 13, an alteration highly restricted to colorectal-derived cancers. A minimal region of amplification on 13q12.2 pinpoints caudal type homeobox transcription factor 2 (CDX2), a regulator of normal intestinal lineage development and differentiation, as a target of the amplification. In contrast to its described role as a colorectal tumor suppressor, CDX2 when amplified is required for the proliferation and survival of colorectal cancer cells. Further, transcriptional profiling, binding-site analysis, and functional studies link CDX2 to Wnt/β-catenin signaling, itself a key oncogenic pathway in colorectal cancer. These data characterize CDX2 as a lineage-survival oncogene deregulated in colorectal cancer. Our findings challenge a prevailing view that CDX2 is a tumor suppressor in colorectal cancer and uncover an additional piece in the multistep model of colorectal tumorigenesis.
Authors:
Keyan Salari; Mary E Spulak; Justin Cuff; Andrew D Forster; Craig P Giacomini; Stephanie Huang; Melissa E Ko; Albert Y Lin; Matt van de Rijn; Jonathan R Pollack
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-10-29
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-02-01     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E3196-205     Citation Subset:  IM    
Affiliation:
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE30475
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cell Survival
Cell Transformation, Neoplastic / genetics,  metabolism*,  pathology
Chromosomes, Human, Pair 13 / genetics,  metabolism
Colorectal Neoplasms / genetics,  metabolism*,  pathology
Disease Models, Animal
Gene Amplification*
Homeodomain Proteins / genetics,  metabolism*
Humans
Mice
NIH 3T3 Cells
Transcription Factors / genetics,  metabolism*
Tumor Suppressor Proteins / genetics,  metabolism*
Wnt Signaling Pathway / genetics
Grant Support
ID/Acronym/Agency:
CA112016/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CDX2 protein, human; 0/Cdx2 protein, mouse; 0/Homeodomain Proteins; 0/Transcription Factors; 0/Tumor Suppressor Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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