title: CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3.
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.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0682, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Chun
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: J G
authors.initials: JG
authors.lastname: Washburn
authors.forename: J W
authors.initials: JW
authors.lastname: MacDonald
authors.forename: K L
authors.initials: KL
authors.lastname: Innes
authors.forename: R
authors.initials: R
authors.lastname: Zhao
authors.forename: M R
authors.initials: MR
authors.lastname: Cruz-Correa
authors.forename: L H
authors.initials: LH
authors.lastname: Dang
authors.forename: D T
authors.initials: DT
authors.lastname: Dang
mesh_terms: D000071616:CDX2 Transcription Factor; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D012097:Repressor Proteins