The prion protein is mainly known for its misfolding and contribution to the neurodegenerative disorder called prion disease. However, the almost ubiquitous tissue expression and conservation of the normal cellular prion protein (PrPC) in mammalian species is suggestive of a significant physiological role. Amongst the proposed cellular roles of PrPC are the regulation of survival, proliferation, adhesion, invasion and migration. Given the positive association of these properties with cancer, it is not surprising that the expression of PrPC is increased in a number of cancer types and that expression levels can be correlated with cancer progression/survival. However, it is not yet known whether the increased expression of PrPC is a consequence of transformation or if it contributes to tumour development.
To investigate this, we have characterised PrPC expression in colorectal cancer cell lines that span the epithelial to mesenchymal spectrum. Consistent with previous reports we observed an increase in the expression of PrPC from cells with a more epithelial phenotype (HT-55) to cells with a more mesenchymal phenotype (SW480), suggesting that PrPC expression levels correlate with tumour progression. In addition, we observed a shift in PrPC processing consistent with the epithelial to mesenchymal transition, with HT-55 cells presenting a greater proportion of cleaved PrPC than SW480 cells.
PrPC processing is known to contribute to its function. We expressed full-length and cleaved PrPC in the DLD-1 colorectal cancer cell line which has a hybrid epithelial/mesenchymal phenotype and displays intermediate levels of PrPC expression and processing. We used this cell line to investigate how PrPC expression and processing affects the phenotype of colorectal cancer cells and to determine whether changes in PrPC expression and processing directly affect the epithelial to mesenchymal transition.