CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3.
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.
Chun
S Y
SY
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0682, USA.
Chen
F
F
Washburn
J G
JG
MacDonald
J W
JW
Innes
K L
KL
Zhao
R
R
Cruz-Correa
M R
MR
Dang
L H
LH
Dang
D T
DT
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
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