The Cellular Prion Protein and the Hallmarks of Cancer

SIMPLE SUMMARY: The cellular prion protein PrP(C) is best known for its involvement, under its pathogenic isoform, in a group of neurodegenerative diseases. Notwithstanding, an emerging role for PrP(C) in various cancer-associated processes has attracted increasing attention over recent years. PrP(C) is overexpressed in diverse types of solid cancers and has been incriminated in various aspects of cancer biology, most notably proliferation, migration, invasion and metastasis, as well as resistance to cytotoxic agents. This article aims to provide a comprehensive overview of the current knowledge of PrP(C) with respect to the hallmarks of cancer, a reference framework encompassing the major characteristics of cancer cells. ABSTRACT: Beyond its causal involvement in a group of neurodegenerative diseases known as Transmissible Spongiform Encephalopathies, the cellular prion protein PrP(C) is now taking centre stage as an important contributor to cancer progression in various types of solid tumours. The prion cancer research field has progressively expanded in the last few years and has yielded consistent evidence for an involvement of PrP(C) in cancer cell proliferation, migration and invasion, therapeutic resistance and cancer stem cell properties. Most recent data have uncovered new facets of the biology of PrP(C) in cancer, ranging from its control on enzymes involved in immune tolerance to its radio-protective activity, by way of promoting angiogenesis. In the present review, we aim to summarise the body of literature dedicated to the study of PrP(C) in relation to cancer from the perspective of the hallmarks of cancer, the reference framework defined by Hanahan and Weinberg.