Journal
BRITISH JOURNAL OF CANCER
Volume 94, Issue 9, Pages 1326-1332Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6603101
Keywords
p300; HCT116; homologous recombination; e-cadherin
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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.
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