The Cellular Prion Protein: A Promising Therapeutic Target for Cancer

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.

Harnessing the Physiological Functions of Cellular Prion Protein in the Kidneys: Applications for Treating Renal Diseases

“…The general functions of PrP C have been extensively investigated via gene knockout experiments. The putative functions associated with PrP C ( Figure 2 A) include the stress response [ 33 , 34 , 35 , 36 ], providing protective effects against oxidative stress [ 37 , 38 , 39 ], cellular differentiation [ 40 , 41 , 42 ], neuronal excitability [ 43 , 44 , 45 ], myelin maintenance [ 46 , 47 , 48 ], circadian rhythm [ 49 , 50 ], metal ion homeostasis [ 51 , 52 , 53 ], modulation of the immune system [ 54 ], the regulation of amyloid beta and tau protein [ 55 ], control of the cellular signaling pathways [ 56 , 57 ], and a few other common cellular processes [ 7 ]. Since PrP C downregulation occurs during the disease incubation period [ 58 ], the loss of normal PrP C function may partly underlie the pathology of prion protein-related diseases, and PrP C could be targeted for therapeutic purposes.…”

“…PrP C -expressing renal adenocarcinoma cells (ACHN cells) demonstrated a modest but statistically significant increase in cell viability compared with the control group via the suppression of TNF-α-induced cell death, and the PrP C expression in ACHN led to a higher proliferative index [ 125 ]. This is interesting, because there is a large volume of research on how PrP C could mediate the tumorigenic effects and promote cancer proliferation, metastasis, drug resistance, and the cancer stem cell phenotype [ 34 ].…”

“…Antibody–drug conjugates are another category of antibody-based therapeutics under active investigation for their application in cancer [ 126 , 194 , 195 , 196 , 197 ], and PrP C may serve as a potential target for antibody–drug conjugates [ 34 ]. Here, aptamers, which are oligonucleotides or peptides that bind to specific target molecules, can be used in lieu of antibodies to create another targeted drug delivery system called aptamer–drug conjugates, as aptamers have a few distinctive advantages over antibodies for their engineering simplicity, rapid tissue penetration, and low immunogenicity [ 198 , 199 , 200 ].…”

PrPC Aptamer Conjugated–Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells

“…The cellular prion protein (PrP C ) is a glycophosphatidylinositol-anchored cell surface protein that is associated with diverse cellular functions, including stress protection and cellular differentiation [ 26 ]. Recently, several studies have shown that PrP C is highly expressed in various types of cancers, including gastric [ 27 ], pancreatic [ 28 ], breast cancers, and CRC [ 29 , 30 ]. Furthermore, it has been reported that PrP C promotes cancer progression by enhancing cancer cell proliferation, metastasis, and drug resistance.…”

“…Furthermore, it has been reported that PrP C promotes cancer progression by enhancing cancer cell proliferation, metastasis, and drug resistance. These results suggest that PrP C is a promising therapeutic target for cancer [ 29 , 30 ]. In this study, we hypothesized that an efficient targeted DDS could be developed for CRC treatment by targeting PrP C .…”