PrP(C) from stem cells to cancer

The cellular prion protein PrP(C) was initially discovered as the normal counterpart of the pathological scrapie prion protein PrP(Sc), the main component of the infectious agent of Transmissible Spongiform Encephalopathies. While clues as to the physiological function of this ubiquitous protein were greatly anticipated from the development of knockout animals, PrP-null mice turned out to be viable and to develop without major phenotypic abnormalities. Notwithstanding, the discovery that hematopoietic stem cells from PrP-null mice have impaired long-term repopulating potential has set the stage for investigating into the role of PrP(C) in stem cell biology. A wealth of data have now exemplified that PrP(C) is expressed in distinct types of stem cells and regulates their self-renewal as well as their differentiation potential. A role for PrP(C) in the fate restriction of embryonic stem cells has further been proposed. Paralleling these observations, an overexpression of PrP(C) has been documented in various types of tumors. In line with the contribution of PrP(C) to stemness and to the proliferation of cancer cells, PrP(C) was recently found to be enriched in subpopulations of tumor-initiating cells. In the present review, we summarize the current knowledge of the role played by PrP(C) in stem cell biology and discuss how the subversion of its function may contribute to cancer progression.