Prion protein: From physiology to cancer biology

Prion protein (PrPc) was originally viewed solely as being involved in prion disease, but now several intriguing lines of evidence have emerged indicating that it plays a fundamental role not only in the nervous system, but also throughout the human body. PrPc is expressed most abundantly in the brain, but has also been detected in other non-neuronal tissues as diverse as lymphoid cells, lung, heart, kidney, gastrointestinal tract, muscle, and mammary glands. Recent data indicate that PrPc may be implicated in biology of glioblastoma, breast cancer, prostate and gastric cancer. Over expression of PrPc is correlated to the acquisition by tumor cells of a phenotype for resistance to cell death induced by TNF alpha and TRAIL or antitumor drugs such as paclitaxel and anthracyclines. PrPc may promote tumorigenesis, proliferation and G1/S transition in gastric cancer cells. This review revisits the physiological functions of PrPc, and its possible implications for cancer biology. (C) 2009 Elsevier Ireland Ltd. All rights reserved.