The purpose of the eukaryotic cell cycle is to accurately duplicate and segregate the genome. Progression through the cell cycle is dependent on a class of proteins called the cyclins and their associated cyclin dependent kinases (cdks). The activity of these reversible switches regulates cell cycle progression to ensure that a DNA synthesis phase (S-phase) always alternates with a chromosome segregation phase (M-phase).

Plakophilin3 (PKP3) is a desmosomal plaque protein that is required for desmosome formation and whose levels are decreased in multiple tumor types, especially in de-differentiated and metastatic tumors. Our results have demonstrated that loss of PKP3 leads to defects in desmosome formation that are accompanied by a decrease in cell-cell adhesion and an increase in migration and invasion, all features of metastatic tumor cells. Indeed, PKP3 loss led to an increase in tumor formation in immunocompromised mice and an increase in metastatic progression.