Function of cellular prion protein (PrPc) in cancer progression has not been elucidated yet. Ectopic expression of PrPc increases the invasion and migration of breast cancer cell line, MCF-7 cells. Over-expressed PrPc increases matrix metalloprotease-9 (MMP-9) expression by enhancing association of NF-kappa B in promoter of MMP-9 gene and ERK signaling in MCF-7 cells. Whereas, silencing of PrPc by siRNA suppresses ERK activation and MMP-9 expression resulting the down-regulation of MD-MB231 cell migration and invasion. Overall, these results suggest that PrPc contribute the breast cancer invasion and migration via MMP-9. (C) 2016 Elsevier Inc. All rights reserved.