Abstract
The cellular prion protein (PrPc) is an evolutionarily conserved cell surface protein encoded by the PRNP gene. PrPc is ubiquitously expressed within nearly all mammalian cells, though most abundantly within the CNS. Besides being implicated in the pathogenesis and transmission of prion diseases, recent studies have demonstrated that PrPc contributes to tumorigenesis by regulating tumor growth, differentiation, and resistance to conventional therapies. In particular, PrPc over-expression has been related to the acquisition of a malignant phenotype of cancer stem cells (CSCs) in a variety of solid tumors, encompassing pancreatic ductal adenocarcinoma (PDAC), osteosarcoma, breast cancer, gastric cancer, and primary brain tumors, mostly glioblastoma multiforme (GBM). Thus, PrPc is emerging as a key in maintaining glioblastoma cancer stem cells’ (GSCs) phenotype, thereby strongly affecting GBM infiltration and relapse. In fact, PrPc contributes to GSCs niche’s maintenance by modulating GSCs’ stem cell-like properties while restraining them from differentiation. This is the first review that discusses the role of PrPc in GBM. The manuscript focuses on how PrPc may act on GSCs to modify their expression and translational profile while making the micro-environment surrounding the GSCs niche more favorable to GBM growth and infiltration.
Highlights
The cellular prion protein (PrPc) is a highly conserved cell surface glycoprotein encoded by the PRNP gene, which is located on the short arm of chromosome 20 [1]
In physiological conditions PrPc expression is seminal for stem cell homeostasis, neurogenesis, and neuronal differentiation, PrPc overexpression may alter pivotal functions of stem cell biology up to sustaining the tumorigenic phenotype of cancer stem cells (CSCs)
This occurs in a variety of tumors including glioblastoma multiforme (GBM), wherein PrPc is emerging as both a prognostic biomarker and active player of cancer biology by promoting CSCs’ self-renewal, stemness, proliferation, and invasiveness and resistance to radio/chemotherapy
Summary
The cellular prion protein (PrPc) is a highly conserved cell surface glycoprotein encoded by the PRNP gene, which is located on the short arm of chromosome 20 [1]. GBM infiltration and therapeutic resistance are mainly due to a subpopulation of highly proliferative CSCs, which are identified as glioblastoma cancer stem cells (GSCs), harboring increased growth rate, self-renewal, pluripotency, and clonogenic potential [22,23]. In the CNS, PrPc regulates neurogenesis by promoting self-renewal, proliferation, and neuronal differentiation of normal neural stem cells (NSCs) (Figure 2) [19,53,54,55]. We discuss evidence on the tumor-promoting role of PrPc in GBM
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