Abstract
Cellular prion protein (PrP(C)) is seminal to modulate a variety of baseline cell functions to grant homeostasis. The classic role of such a protein was defined as a chaperone-like molecule being able to rescue cell survival. Nonetheless, PrP(C) also represents the precursor of the deleterious misfolded variant known as scrapie prion protein (PrP(Sc)). This variant is detrimental in a variety of prion disorders. This multi-faceted role of PrP is greatly increased by recent findings showing how PrP(C) in its folded conformation may foster tumor progression by acting at multiple levels. The present review focuses on such a cancer-promoting effect. The manuscript analyzes recent findings on the occurrence of PrP(C) in various cancers and discusses the multiple effects, which sustain cancer progression. Within this frame, the effects of PrP(C) on stemness and differentiation are discussed. A special emphasis is provided on the spreading of PrP(C) and the epigenetic effects, which are induced in neighboring cells to activate cancer-related genes. These detrimental effects are further discussed in relation to the aberrancy of its physiological and beneficial role on cell homeostasis. A specific paragraph is dedicated to the role of PrP(C) beyond its effects in the biology of cancer to represent a potential biomarker in the follow up of patients following surgical resection.