Abstract
Cellular prion protein (PrP(C)) is a membrane-anchored glycoprotein representing the physiological counterpart of PrP scrapie (PrP(Sc)), which plays a pathogenetic role in prion diseases. Relatively little information is however available about physiological role of PrP(C). Although PrP(C) ablation in mice does not induce lethal phenotypes, impairment of neuronal and bone marrow plasticity was reported in embryos and adult animals. In neurons, PrP(C) stimulates neurite growth, prevents oxidative stress-dependent cell death, and favors antiapoptotic signaling. However, PrP(C) activity is not restricted to post-mitotic neurons, but promotes cell proliferation and migration during embryogenesis and tissue regeneration in adult. PrP(C) acts as scaffold to stabilize the binding between different membrane receptors, growth factors, and basement proteins, contributing to tumorigenesis. Indeed, ablation of PrP(C) expression reduces cancer cell proliferation and migration and restores cell sensitivity to chemotherapy. Conversely, PrP(C) overexpression in cancer stem cells (CSCs) from different tumors, including gliomas-the most malignant brain tumors-is predictive for poor prognosis, and correlates with relapses. The mechanisms of the PrP(C) role in tumorigenesis and its molecular partners in this activity are the topic of the present review, with a particular focus on PrP(C) contribution to glioma CSCs multipotency, invasiveness, and tumorigenicity.