| CDX2 is an amplified lineage-survival oncogene in colorectal cancer. | |
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MedLine Citation:
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PMID: 23112155 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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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:
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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:
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Created Date: 2012-11-15 Completed Date: 2013-02-01 Revised Date: 2013-05-13 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: E3196-205 Citation Subset: IM |
Affiliation:
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Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE30475 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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CA112016/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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
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