1. ¹Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
2. ²The University of Michigan Comprehensive Cancer Center Affymetrix and cDNA Microarray Core Facility, Ann Arbor, MI, USA
3. ³Department of Internal Medicine, Division of Gastroenterology, The University of Puerto Rico Comprehensive Cancer Center, San Juan, PR, USA
4. ⁴The University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
5. ⁵Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

Correspondence: DT Dang, Division of Gastroenterology, Department of Internal Medicine University of Michigan, 1150 W. Medical Center Drive, MSRB I, Room 6514, Ann Arbor, MI 48109-0682, USA. E-mail: dangd@umich.edu

⁶These authors contributed equally to this work.

Received 21 October 2006; Revised 28 November 2006; Accepted 1 December 2006; Published online 5 February 2007.

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.