CDX2 is an amplified lineage-survival oncogene in colorectal cancer
| Autor: | Craig P. Giacomini, Andrew D. Forster, Matt van de Rijn, Keyan Salari, Jonathan R. Pollack, Mary E. Spulak, Albert Lin, Melissa E. Ko, Stephanie Huang, Justin Cuff |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Deleted in Colorectal Cancer
Colorectal cancer Cell Survival Biology Mouse model of colorectal and intestinal cancer medicine.disease_cause Mice Cell Line Tumor medicine Animals Humans CDX2 Transcription Factor CDX2 Transcription factor Wnt Signaling Pathway Homeodomain Proteins Multidisciplinary Oncogene Chromosomes Human Pair 13 Tumor Suppressor Proteins Wnt signaling pathway Gene Amplification medicine.disease Molecular biology Disease Models Animal Cell Transformation Neoplastic PNAS Plus Cancer research NIH 3T3 Cells Carcinogenesis Colorectal Neoplasms Transcription Factors |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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