The Cellular Prion Protein and the Hallmarks of Cancer

Mouillet-Richard, Sophie; Ghazi, Alexandre; Laurent‐Puig, Pierre

doi:10.3390/cancers13195032

Cited by 15 publications

(10 citation statements)

References 123 publications

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“…A set of studies have allowed to uncover a link between PrP C and cancer [ 6 ]. For instance, we recently showed that PrP C is overexpressed in the poor-prognosis subtype of colon cancer and that it controls the expression of a set of genes associated with a mesenchymal phenotype [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer

et al. 2022

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The cellular prion protein PrPC partners with caveolin-1 (CAV1) in neurodegenerative diseases but whether this interplay occurs in cancer has never been investigated. By leveraging patient and cell line datasets, we uncover a molecular link between PrPC and CAV1 across cancer. Using cell-based assays, we show that PrPC regulates the expression of and interacts with CAV1. PrPC additionally controls the expression of the amyloid precursor protein APP and of the Aβ generating enzyme BACE1, and regulates the levels of Aβ, whose accumulation is a central event in Alzheimer’s disease. We further identify DKK1 and DKK3, involved in both Alzheimer’s disease and cancer progression, as targets of the PrPC-dependent axis. Finally, we establish that antibody-mediated blocking of the Aβ-PrPC interaction delays the growth of prostate cancer cell line-derived xenografts and prevents the development of metastases. Our data additionally support an enrichment of the Aβ-PrPC-dependent pathway in the basal subtype of prostate cancer, associated with anti-hormonal therapy resistance, and in mesenchymal colon cancer, associated with poor prognosis. Thus, based on a parallel with neurodegenerative diseases, our results bring to light an Aβ-PrPC axis and support the potential of targeting this pathway in patients with selected subtypes of prostate and colon cancer.

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Section: Introductionmentioning

confidence: 99%

A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer

et al. 2022

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“…PrPC is a glycosyl-phosphatidylinositol-anchored cell surface protein, which is related to a variety of cell functions ( Mouillet-Richard et al, 2021 ). The PrPC gene is highly expressed in a variety of cancers, including colorectal cancer (CRC), according to recent studies ( Yun et al, 2021 ).…”

Section: Aptamer-conjugated Aunps For Cancer Therapeuticsmentioning

confidence: 99%

Aptamer-conjugated gold nanoparticles and their diagnostic and therapeutic roles in cancer

Deng

Luo

et al. 2023

Front. Bioeng. Biotechnol.

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The burden of incidence rate and mortality of cancer is increasing rapidly, and the development of precise intervention measures for cancer detection and treatment will help reduce the burden and pain of cancer. At present, the sensitivity and specificity of tumor markers such as CEA and CA-125 used clinically are low, while PET, SPECT, and other imaging diagnoses with high sensitivity possess shortcomings, including long durations to obtain formal reports and the inability to identify the molecular pathological type of cancer. Cancer surgery is limited by stage and easy to recur. Radiotherapy and chemotherapy often cause damage to normal tissues, leading to evident side effects. Aptamers can selectively and exclusively bind to biomarkers and have, therefore, gained attention as ligands to be targeted for cancer detection and treatment. Gold nanoparticles (AuNPs) are considered as promising nano carriers for cancer diagnosis and treatment due to their strong light scattering characteristics, effective biocompatibility, and easy surface modification with targeted agents. The aptamer-gold nanoparticles targeting delivery system developed herein can combine the advantages of aptamers and gold nanoparticles, and shows excellent targeting, high specificity, low immunogenicity, minor side effects, etc., which builds a bridge for cancer markers to be used in early and efficient diagnosis and precise treatment. In this review, we summarize the latest progress in the application of aptamer-modified gold nanoparticles in cancer targeted diagnosis and delivery of therapeutic agents to cancer cells and emphasize the prospects and challenges of transforming these studies into clinical applications.

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“…PRNP knockout (KO) experimental models have provided some insights into the physiological function of “prion-like” but did not evidence direct alterations. This factor indicates that other molecules can physiologically compensate the PrPC loss of function [ 26 ]. Despite this finding, by analyzing only the activity in cell physiology, it seems that PrPC protects neurons against cell death and oxidative stress, controls copper metabolism, synaptic transmission, and cell adhesion, and seems to be involved in maintaining the cellular cycle to activate the immune response [ 5 ].…”

Section: The Role Of Prion Proteinmentioning

confidence: 99%

The Role of Cellular Prion Protein in Glioma Tumorigenesis Could Be through the Autophagic Mechanisms: A Narrative Review

Armocida

Busceti

Biagioni

et al. 2023

IJMS

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The carcinogenesis of glial tumors appears complex because of the many genetic and epigenetic phenomena involved. Among these, cellular prion protein (PrPC) is considered a key factor in cell-death resistance and important aspect implicated in tumorigenesis. Autophagy also plays an important role in cell death in various pathological conditions. These two cellular phenomena are related and share the same activation by specific alterations in the cellular microenvironment. Furthermore, there is an interdependence between autophagy and prion activity in glioma tumorigenesis. Glioma is one of the most aggressive known cancers, and the fact that such poorly studied processes as autophagy and PrPC activity are so strongly involved in its carcinogenesis suggests that by better understanding their interaction, more can be understood about its origin and treatment. Few studies in the literature relate these two cellular phenomena, much less try to explain their combined activity and role in glioma carcinogenesis. In this study, we explored the recent findings on the molecular mechanism and regulation pathways of autophagy, examining the role of PrPC in autophagy processes and how they may play a central role in glioma tumorigenesis. Among the many molecular interactions that PrP physiologically performs, it appears that processes shared with autophagy activity are those most implicated in glial tumor carcinogeneses such as activity on MAP kinases, PI3K, and mTOR. This work can be supportive and valuable as a basis for further future studies on this topic.

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The Cellular Prion Protein and the Hallmarks of Cancer

Cited by 15 publications

References 123 publications

A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer

A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer

Aptamer-conjugated gold nanoparticles and their diagnostic and therapeutic roles in cancer

The Role of Cellular Prion Protein in Glioma Tumorigenesis Could Be through the Autophagic Mechanisms: A Narrative Review

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