Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition

Area of Science:

• Molecular Biology
• Cancer Research
• Epigenetics

Background:

• p300 is a crucial transcriptional cofactor and histone acetyltransferase regulating diverse cellular functions.
• Histone acetylation by p300 plays a significant role in gene expression and cellular processes.
• Understanding p300's role in cancer progression is vital for therapeutic development.

Purpose of the Study:

• To investigate the functional consequences of p300 deficiency in colon carcinoma cells.
• To determine the impact of p300 loss on epithelial to mesenchymal transition (EMT)-like phenotypes.
• To elucidate the relationship between p300, cell adhesion, and cancer cell migration.

Main Methods:

• Gene targeting was employed to generate p300-deficient (p300-) HCT116 colon carcinoma cells.
• Proteomic and transcriptomic analyses compared p300- cells with parental HCT116 cells.
• Cell adhesion assays (cell-cell and cell-matrix) and migration assays (collagen and Matrigel) were performed.

Main Results:

• p300- cells exhibited differential regulation of genes involved in cell-extracellular matrix interactions, characteristic of EMT.
• Loss of p300 resulted in aggressive cancer phenotypes, including reduced cell-cell and cell-matrix adhesion.
• p300- cells showed increased migration, which was metalloproteinase-mediated despite downregulation of key metalloproteinases.

Conclusions:

• p300 deficiency drives aggressive cancer phenotypes in colon carcinoma cells.
• Altered cellular adhesion properties in p300- cells are critical determinants of enhanced cellular mobility.
• These findings underscore the importance of p300 in maintaining normal cellular adhesion and suppressing cancer aggressiveness.