1. ¹Department of Oncology, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK
2. ²Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK
3. ³Department of Anatomy, University of British Columbia, 2177 Westbrook Mall, Vancouver BC V66T 1Z3, UK

Correspondence: Professor G Murphy, E-mail: gm290@cam.ac.uk

Received 1 December 2005; Revised 9 March 2006; Accepted 15 March 2006; Published online 18 April 2006.

Abstract

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.