ArticleThe American journal of pathology2016
Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- 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
- Upregulated PrPNPJ precision oncology · 2024Article
- PrPOncogene · 2024Article
- The Humanization and Maturation of an Anti-PrPc Antibody.Bioengineering (Basel, Switzerland) · 2024Article
- Loss of HES1 expression is associated with extracellular matrix remodeling and tumor immune suppression in KRAS mutant colon adenocarcinomas.Scientific reports · 2023Article
- Emerging roles of the cellular prion protein (PrPCellular and molecular life sciences : CMLS · 2023Review
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- The Role of Cellular Prion Protein in Glioma Tumorigenesis Could Be through the Autophagic Mechanisms: A Narrative Review.International journal of molecular sciences · 2023Review
- Article
- The multiple functions of PrPJournal of molecular medicine (Berlin, Germany) · 2022Review
- Cellular Prion Protein Is Closely Associated with Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2022Article
- 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
- 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
- The Cellular Prion Protein: A Promising Therapeutic Target for Cancer.International journal of molecular sciences · 2020Review
- Prion Protein at the Leading Edge: Its Role in Cell Motility.International journal of molecular sciences · 2020Review
Corrections and comments
- Erratum issuedCorrection.2017
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Up-regulation of human prion protein (PrP) in patients with pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis. However, the underlying molecular mechanism of PrP-mediated tumorigenesis is not completely understood. In this study, we found that PDAC cell lines can be divided into either PrP high expresser or PrP low expresser. In addition to filamin A (FLNA), PrP interacts with Notch1, forming a PrP/FLNA/Notch1 complex. Silencing PrP in high-expresser cells decreases Notch1 expression and Notch1 signaling. These cells exhibited decreased proliferation, xenograft growth, and tumor invasion but show increased tumor apoptosis. These phenotypes were rescued by ectopically expressed and activated Notch1. By contrast, overexpression of PrP in low expressers increases Notch1 expression and signaling, enhances proliferation, and increases tumor invasion and xenograft growth that can be blocked by a Notch inhibitor. Our data further suggest that PrP increases Notch1 stability likely through suppression of Notch proteosome degradation. Additionally, we found that targeting PrP combined with anti-Notch is much more effective than singularly targeted therapy in retarding PDAC growth. Finally, we show that coexpression of PrP and Notch1 confers an even poorer prognosis than PrP expression alone. Taken together, our results have unraveled a novel molecular pathway driven by interactions between PrP and Notch1 in the progression of PDAC, supporting a critical tumor-promoting role of Notch1 in PrP-expressing PDAC tumors.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.