A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion.
A thorough understanding of histone acetyltransferase CBP/p300-mediated regulation of gene expression and cell growth is essential to identify mechanisms relevant to the development of histone deacetylase (HDAC) inhibitor-based preventive and therapeutic strategies. We found that knockdown of CBP/p300 interacting coactivator with glutamic acid/aspartic acid-rich tail 2 (CITED2) increased colon cancer cell invasiveness in vitro. Gene expression profiling revealed that CITED2 knockdown induced matrix metalloproteinase-13 (MMP-13) gene expression in colon cancer cells. Butyrate, a naturally occurring HDAC inhibitor, induced CITED2 expression and downregulated MMP-13 expression in RKO cells. Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2 regulates colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer.
Bai
Longchuan
L
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Merchant
Juanita L
JL
D002087:Butyrates / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
D002087:Butyrates; C486381:CITED2 protein, human; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D053509:Matrix Metalloproteinase 13