title: Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition.
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.
authors.affiliation: Department of Oncology, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
authors.forename: D
authors.initials: D
authors.lastname: Krubasik
authors.forename: N G
authors.initials: NG
authors.lastname: Iyer
authors.forename: W R
authors.initials: WR
authors.lastname: English
authors.forename: A A
authors.initials: AA
authors.lastname: Ahmed
authors.forename: M
authors.initials: M
authors.lastname: Vias
authors.forename: C
authors.initials: C
authors.lastname: Roskelley
authors.forename: J D
authors.initials: JD
authors.lastname: Brenton
authors.forename: C
authors.initials: C
authors.lastname: Caldas
authors.forename: G
authors.initials: G
authors.lastname: Murphy
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D004338:Drug Combinations; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells; D005109:Extracellular Matrix / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D007797:Laminin; D008648:Mesoderm; D045726:Metalloproteases / Q000096:biosynthesis / Q000378:metabolism; D010641:Phenotype; D011509:Proteoglycans
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D045726:Metalloproteases