Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition.
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.
Krubasik
D
D
Department of Oncology, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
Iyer
N G
NG
English
W R
WR
Ahmed
A A
AA
Vias
M
M
Roskelley
C
C
Brenton
J D
JD
Caldas
C
C
Murphy
G
G
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
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D045726:Metalloproteases