Document Detail

CDX2 is an amplified lineage-survival oncogene in colorectal cancer.
MedLine Citation:
PMID:  23112155     Owner:  NLM     Status:  MEDLINE    
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.
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
Related Documents :
23939375 - Overcoming platinum resistance in preclinical models of ovarian cancer using the neddyl...
24963475 - Exosome in tumour microenvironment: overview of the crosstalk between normal and cancer...
20440265 - Cancer-selective apoptotic effects of extracellular and intracellular par-4.
23500545 - Oxysterols in cancer cell proliferation and death.
9773215 - Endoscopic mucosal resection for esophageal and gastric mucosal cancers.
9492245 - Remission of cancer chemotherapy-induced emesis during antidepressant therapy with nefa...
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    
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Data Bank Information
Bank Name/Acc. No.:
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
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*
NIH 3T3 Cells
Transcription Factors / genetics,  metabolism*
Tumor Suppressor Proteins / genetics,  metabolism*
Wnt Signaling Pathway / genetics
Grant Support
Reg. No./Substance:
0/CDX2 protein, human; 0/Cdx2 protein, mouse; 0/Homeodomain Proteins; 0/Transcription Factors; 0/Tumor Suppressor Proteins

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

Previous Document:  Immunoglobulin-like transcript receptors on human dermal CD14+ dendritic cells act as a CD8-antagoni...
Next Document:  Stochastic effects are important in intrahost HIV evolution even when viral loads are high.