Abstract
CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. We have reported that CDX2 promotes tumorigenicity in a subset of human colorectal cancer cell lines. Here, we present evidence that CDX2 negatively regulates the well-documented growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3). Specifically, CDX2 binds to the IGFBP-3 gene promoter and can repress IGFBP-3 transcription, protein expression and secretion. Furthermore, inhibition of IGFBP-3 partially rescues the decreased anchorage-independent growth phenotype observed in CDX2 knockout cells. These data demonstrate for the first time that (1) CDX2 can function as a transcriptional repressor, and (2) one mechanism by which CDX2 promotes anchorage-independent growth is by transcriptional repression of IGFBP-3.
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Acknowledgements
DTD was supported by NIH Grant K08DK59970, AGA Research Scholar Award, and GIDH Basic Research Award; LHD by NIH Grant K22CA111897; JWM, JGW, and KLI by NIH University of Michigan Cancer Center Support Grant 5 P30 CA46592
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
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Chun, S., Chen, F., Washburn, J. et al. CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3. Oncogene 26, 4725–4729 (2007). https://doi.org/10.1038/sj.onc.1210258
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DOI: https://doi.org/10.1038/sj.onc.1210258
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