CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3

S. Y. Chun, F. Chen, J. G. Washburn, J. W. MacDonald, K. L. Innes, R. Zhao, M. R. Cruz-Correa, L. H. Dang, D. T. Dang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4725-4729
Number of pages5
JournalOncogene
Volume26
Issue number32
DOIs
StatePublished - Jul 12 2007
Externally publishedYes

Keywords

  • Anchorage-independent growth
  • CDX2
  • Colorectal cancer
  • IGFBP-3

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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