ArticleJCI insight2019
Secreted cellular prion protein binds doxorubicin and correlates with anthracycline resistance in breast cancer.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Proteolytic shedding of the prion protein: Uncovering "new" biological implications of a conserved cleavage event.Neural regeneration research · 2026Article
- ADAM10-Mediated Proteolytic Remodelling of Signalling and Adhesion Proteins on Brain Cell-Derived Small Extracellular Vesicles.Journal of extracellular biology · 2026Article
- High cellular prion protein expression in cholangiocarcinoma: A marker for early postoperative recurrence and unfavorable prognosis.World journal of gastrointestinal surgery · 2025Article
- Integrated multi-omics elucidatesFrontiers in immunology · 2025Article
- Re-evaluation of the relationship between PrPc expression and patient prognosis in primary esophageal squamous cell carcinoma and primary hepatocellular carcinoma.Scientific reports · 2024Article
- Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.Acta neuropathologica · 2024Article
- The Humanization and Maturation of an Anti-PrPc Antibody.Bioengineering (Basel, Switzerland) · 2024Article
- A Potential biomarker for the early diagnosis of OSCC: saliva and serum PrPJournal of Cancer · 2024Article
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- Construct ceRNA Network and Risk Model of Breast Cancer Using Machine Learning Methods under the Mechanism of Cuproptosis.Diagnostics (Basel, Switzerland) · 2023Article
- Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.Molecules (Basel, Switzerland) · 2022Review
- Detailing the ultrastructure's increase of prion protein in pancreatic adenocarcinoma.World journal of gastroenterology · 2021Article
- The Cellular Prion Protein and the Hallmarks of Cancer.Cancers · 2021Review
- Tumor resistance to radiotherapy is triggered by an ATM/TAK1-dependent-increased expression of the cellular prion protein.Oncogene · 2021Article
- Involvement of Cellular Prion Protein in Invasion and Metastasis of Lung Cancer by Inducing Treg Cell Development.Biomolecules · 2021Article
- The Role of Cellular Prion Protein in Promoting Stemness and Differentiation in Cancer.Cancers · 2021Review
- The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target.Frontiers in oncology · 2021Review
- Tradeoff between metabolic i-proteasome addiction and immune evasion in triple-negative breast cancer.Life science alliance · 2020Article
- Pathogenic Prion Protein Isoforms Are Not Present in Cerebral Organoids Generated from Asymptomatic Donors Carrying the E200K Mutation Associated with Familial Prion Disease.Pathogens (Basel, Switzerland) · 2020Article
- Clinicopathologic significance of nuclear HER4 and phospho-YAP(STherapeutic advances in medical oncology · 2020Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anthracyclines are amongst the most effective chemotherapeutics ever developed, but they produce grueling side-effects, serious adverse events and resistance often develops over time. We found that these compounds can be sequestered by secreted cellular Prion protein (PrPC), blocking their cytotoxic activity. This effect was dose-dependent using either cell line-conditioned medium or human serum as a source of PrPC. Genetic depletion of PrPC or inhibition of binding via chelation of ionic copper prevented the interaction and restored cytotoxic activity. This was more pronounced for doxorubicin than its epimer, epirubicin. Investigating the relevance to breast cancer management, we found that the levels of PRNP transcript in pre-treatment tumor biopsies stratified relapse-free survival after neoadjuvant treatment with anthracyclines, particularly amongst doxorubicin-treated patients with residual disease at surgery (p=2.8E-08). These data suggest that local sequestration could mediate treatment resistance. Consistent with this, tumor cell expression of PrPC protein correlated with poorer response to doxorubicin but not epirubicin in an independent cohort analyzed by immunohistochemistry, particularly soluble isoforms released into the extracellular environment by shedding (p=0.015). These findings have important potential clinical implications for frontline regimen decision-making. We suggest there is warranted utility for prognostic PrPC/PRNP assays to guide chemo-sensitization strategies that exploit an understanding of PrPC-anthracycline-copper ion complexes.
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