Functions of the Prion Protein

Hirsch, Théo Z.; Martin-Lannerée, Séverine; Mouillet-Richard, Sophie

doi:10.1016/bs.pmbts.2017.06.001

Cited by 23 publications

(32 citation statements)

References 244 publications

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“…One emerging regulator of CSC function is the cellular prion protein PrP C [8], which is infamous for its involvement in a group of neurodegenerative diseases under its pathogenic scrapie isoform [9]. PrP C is a ubiquitous protein mainly found as a GPI-anchored cell surface molecule and also present in the extracellular space as a soluble isoform [10]. PrP C can interact with promiscuous partners and mobilize cell signalling cascades [10], which make it an interesting candidate to sense the tumour microenvironment and foster an adaptive response in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…PrP C is a ubiquitous protein mainly found as a GPI-anchored cell surface molecule and also present in the extracellular space as a soluble isoform [10]. PrP C can interact with promiscuous partners and mobilize cell signalling cascades [10], which make it an interesting candidate to sense the tumour microenvironment and foster an adaptive response in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer

et al. 2019

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Background Comprehensive transcriptomic analyses have shown that colorectal cancer (CRC) is heterogeneous and have led to the definition of molecular subtypes among which the stem-cell, mesenchymal-like group is associated with poor prognosis. The molecular pathways orchestrating the emergence of this subtype are incompletely understood. In line with the contribution of the cellular prion protein PrP C to stemness, we hypothesize that deregulation of this protein could lead to a stem-cell, mesenchymal-like phenotype in CRC. Methods We assessed the distribution of the PrP C -encoding PRNP mRNA in two large CRC cohorts according to molecular classification and its association with patient survival. We developed cell-based assays to explore the impact of gain and loss of PrP C function on markers of the mesenchymal subtype and to delineate the signalling pathways recruited by PrP C . We measured soluble PrP C in the plasmas of 325 patients with metastatic CRC and probed associations with disease outcome. Findings We found that PRNP gene expression is enriched in tumours of the mesenchymal subtype and is associated with poor survival. Our in vitro analyses revealed that PrP C controls the expression of genes that specify the mesenchymal subtype through the recruitment of the Hippo pathway effectors YAP and TAZ and the TGFß pathway. We showed that plasma levels of PrP C are elevated in metastatic CRC and are associated with poor disease control. Interpretation Our findings define PrP C as a candidate driver of the poor-prognosis mesenchymal subtype of CRC. They suggest that PrP C may serve as a potential biomarker for patient stratification in CRC. Funding Grant support was provided by the following: (grant number 2016-1-EMERG-36-UP 5-1), (grant number PJA 20171206220), (grant number 415) as well as .

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer

et al. 2019

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“…PrP C is located within lipid rafts [3,4], sphingolipid-rich membrane micro domains, and it is present in several kind of cells such as neural and lymphocytic cells [5,6,7]. The membrane-bound isoform can act as a cell surface receptor, or as a co-receptor, recruiting downstream signal transduction pathways [8,9,10,11]. PrP C is involved in a wide range of cellular processes, such as synaptic plasticity, neurite regulation, calcium homeostasis, copper metabolism, apoptosis and cellular resistance to oxidative stress [12,13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Cellular and Molecular Mechanisms Mediated by recPrPC Involved in the Neuronal Differentiation Process of Mesenchymal Stem Cells

Martellucci

Santacroce²,

Santilli

et al. 2019

IJMS

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Human Dental Pulp Stem Cells (hDPSCs) represent a type of adult mesenchymal stem cells that have the ability to differentiate in vitro in several lineages such as odontoblasts, osteoblasts, chondrocytes, adipocytes and neurons. In the current work, we used hDPSCs as the experimental model to study the role of recombinant prion protein 23–231 (recPrPC) in the neuronal differentiation process, and in the signal pathway activation of ERK 1/2 and Akt. We demonstrated that recPrPC was able to activate an intracellular signal pathway mediated by extracellular-signal-regulated kinase 1 and 2 (ERK 1/2) and protein kinase B (Akt). Moreover, in order to understand whether endogenous prion protein (PrPC) was necessary to mediate the signaling induced by recPrPC, we silenced PrPC, demonstrating that the presence of endogenous PrPC was essential for ERK 1/2 and Akt phosphorylation. Since endogenous PrPC is a well-known lipid rafts component, we evaluated the role of these structures in the signal pathway induced by recPrPC. Our results suggest that lipid rafts integrity play a key role in recPrPC activity. In fact, lipid rafts inhibitors, such as fumonisin B1 and MβCD, significantly prevented ERK 1/2 and Akt phosphorylation induced by recPrPC. In addition, we investigated the capacity of recPrPC to induce hDPSCs neuronal differentiation process after long-term stimulation through the evaluation of typical neuronal markers expression such as B3-Tubulin, neurofilament-H (NFH) and growth associated protein 43 (GAP43). Accordingly, when we silenced endogenous PrPC, we observed the inhibition of neuronal differentiation induced by recPrPC. The combined data suggest that recPrPC plays a key role in the neuronal differentiation process and in the activation of specific intracellular signal pathways in hDPSCs.

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“…This would fit in with the protective role ascribed to PrP C in the context of various types of stresses (see ref. 9 for review). Conversely, in the context of CKD, our results suggest that high PrP C levels are associated with worse renal function.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we investigated if the soluble form of the ER stress-inducible protein, prion protein (PrP C ) is also a candidate urinary ER stress biomarker. The cellular prion protein PrP C , which is involved in the pathophysiology of some neurodegenerative diseases under its pathogenic scrapie isoform, is a ubiquitous protein mainly found as a GPI-anchored cell surface molecule and present in the extracellular space as a soluble isoform 9 . The aim of this study was to determine whether PrP C could serve as a urinary ER stress biomarker for ER stress-mediated kidney diseases by studying a combination of cellular models and human patient samples.…”

Section: Introductionmentioning

confidence: 99%

The cellular prion protein is a stress protein secreted by renal tubular cells and a urinary marker of kidney injury

et al. 2020

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Endoplasmic Reticulum (ER) stress underlies the pathogenesis of numerous kidney diseases. A better care of patients with kidney disease involves the identification and validation of ER stress biomarkers in the early stages of kidney disease. For the first time to our knowledge, we demonstrate that the prion protein PrP C is secreted in a conventional manner by ER-stressed renal epithelial cell under the control of the transcription factor x-box binding protein 1 (XBP1) and can serve as a sensitive urinary biomarker for detecting tubular ER stress. Urinary PrP C elevation occurs in patients with chronic kidney disease. In addition, in patients undergoing cardiac surgery, detectable urine levels of PrP C significantly increase after cardiopulmonary bypass, a condition associated with activation of the IRE1-XBP1 pathway in the kidney. In conclusion, our study has identified PrP C as a novel urinary ER stress biomarker with potential utility in early diagnosis of ongoing acute or chronic kidney injury.

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Functions of the Prion Protein

Cited by 23 publications

References 244 publications

The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer

The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer

Cellular and Molecular Mechanisms Mediated by recPrPC Involved in the Neuronal Differentiation Process of Mesenchymal Stem Cells

The cellular prion protein is a stress protein secreted by renal tubular cells and a urinary marker of kidney injury

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