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p300 is a transcriptional cofactor and prototype histone acetyltransferase involved in regulating multiple cellular processes. We generated p300 deficient (p300-) cells from the colon carcinoma cell line HCT116 by gene targeting. Comparison of epithelial and mesenchymal proteins in p300- with parental HCT116 cells showed that a number of genes involved in cell and extracellular matrix interactions, typical of 'epithelial to mesenchyme transition' were differentially regulated at both the RNA and protein level. p300- cells were found to have aggressive 'cancer' phenotypes, with loss of cell-cell adhesion, defects in cell-matrix adhesion and increased migration through collagen and matrigel. Although migration was shown to be metalloproteinase mediated, these cells actually showed a downregulation or no change in the level of key metalloproteinases, indicating that changes in cellular adhesion properties can be critical for cellular mobility.

Original publication

DOI

10.1038/sj.bjc.6603101

Type

Journal article

Journal

Br J Cancer

Publication Date

08/05/2006

Volume

94

Pages

1326 - 1332

Keywords

Cell Adhesion, Cell Movement, Cell Transformation, Neoplastic, Collagen, Down-Regulation, Drug Combinations, E1A-Associated p300 Protein, Epithelial Cells, Extracellular Matrix, HCT116 Cells, Humans, Laminin, Mesoderm, Metalloproteases, Phenotype, Proteoglycans