Abstract
Studies on the cellular prion protein (PrPC) have been actively conducted because misfolded PrPC is known to cause transmissible spongiform encephalopathies or prion disease. PrPC is a glycophosphatidylinositol-anchored cell surface glycoprotein that has been reported to affect several cellular functions such as stress protection, cellular differentiation, mitochondrial homeostasis, circadian rhythm, myelin homeostasis, and immune modulation. Recently, it has also been reported that PrPC mediates tumor progression by enhancing the proliferation, metastasis, and drug resistance of cancer cells. In addition, PrPC regulates cancer stem cell properties by interacting with cancer stem cell marker proteins. In this review, we summarize how PrPC promotes tumor progression in terms of proliferation, metastasis, drug resistance, and cancer stem cell properties. In addition, we discuss strategies to treat tumors by modulating the function and expression of PrPC via the regulation of HSPA1L/HIF-1α expression and using an anti-prion antibody.
Highlights
The cellular prion protein (PrPC) is a cell surface glycophosphatidylinositol (GPI)-anchored protein consisting of 208 amino acids, and it is encoded by the PRNP gene located on chromosome 20
We summarize the role of PrPC in tumor progression in terms of proliferation, metastasis, drug resistance, and cancer stem cell properties
Several studies have suggested that PrPC promotes tumor progression
Summary
The cellular prion protein (PrPC) is a cell surface glycophosphatidylinositol (GPI)-anchored protein consisting of 208 amino acids, and it is encoded by the PRNP gene located on chromosome 20. Several studies have shown that PrPC expression is associated with tumor progression [11,12,13,14,15]. PrPC is first synthesized as a precursor protein (pre-pro-PrP) comprising 253 amino acids with a signal peptide at the N-terminus and a GPI anchor peptide signaling sequence (GPI-PSS) at the C-terminus. Not all PrPCs are present on the cell surface They are constantly internalized through the recycling endosome and trafficked back repeatedly [20,21,22]. It is well established that PrPC is involved in the main aspects of cancer biology: proliferation, metastasis, and drug resistance. We summarize the role of PrPC in tumor progression in terms of proliferation, metastasis, drug resistance, and cancer stem cell properties. We discuss strategies to control tumor growth by regulating the function and expression of PrPC
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