14-3-3σ is expressed only in cells of epithelial origin and loss of 14-3-3σ has been observed in multiple solid tumors suggesting that it functions as a tumor suppressor. However, the mechanisms by which 14-3-3σ loss leads to tumor progression are not understood. The experiments in this report demonstrate that loss of 14-3-3σ leads to an induction of the epithelial to mesenchymal transition (EMT). The EMT was accompanied by an increase in epithelial markers, a decrease in mesenchymal markers and an increase in migration and invasion were observed in the 14-3-3σ -/- cells.

Work in the laboratory has led to the development of a novel method for the generation of transgenic animals. US and Indian patent applications for the process have been filed and the protocol has been published. Further, our work has shown that loss of 14-3-3γ leads to sterility in male mice due to a defect in desmosome formation between sertoli cells and also between Sertoli cells and spermatocytes. The loss of adhesion seems to be due to a decrease in desomosome formation, due to a defect in the transport of the desmosomal plaque protein, plakoglobin (PG), to the cell border.

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.