Tumor necrosis factor-α-converting enzyme (TACE/ADAM-17) mediates the ectodomain cleavage of intercellular adhesion molecule-1 (ICAM-1)

Nina L. Tsakadze, Srinivas D. Sithu, Utpal Sen, William R. English, Gillian Murphy, Stanley E. D'Souza

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)3157-3164
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number6
DOIs
Publication statusPublished - Feb 2006

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