Prion Protein In Pancreatic Ductal Adenocarcinoma | 16441
Journal of Clinical & Experimental Pathology
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The cellular prion protein (PrP) is a GPI-anchored membrane protein mainly known for its role in fatal neurodegenerative
diseases. The mutated form of PrP is the infectious agent of prion disease. The normal PrP protein can be found on
many types of normal cells. Our recent data showed that PrP are over-expressed in a subset of human pancreatic ductal
adenocarcinoma (PDAC), and the up-regulated PrP exist as a Pro-PrP instead of a mature GPI-anchored PrP. The Pro-PrP
has a motif binding filament A, and subsequently disrupts the normal cell skeleton and involves carcinogenesis by facilitating
cellular adhesion, migration and invasion. Most importantly, the up-regulation of PrP is a marker of poorer prognosis in PDAC.
Recently we found that high PrP expressions in various PDAC cell lines regulate Notch signaling pathway, by up-regulation of
the activated Notch1 intracellular domain (NICD), which could form a complex with PrP. The silencing of either component
led to the down-regulation of the other partner. Knockdown of PrP in PDAC cell lines induced cancer cell apoptosis, decreased
cell invasion and Akt activation, while over-expression of PrP in PDAC cells led to increased NICD and Akt phosphorylation,
promoted cell proliferation and invasion. These findings suggest that PrP in certain pancreatic cancer cells promotes tumor
survival and invasion through regulating Notch signaling and Akt activation pathway. Future studies will aim to elucidate the
mechanisms underlying the cross-talk between PrP and Notch in pancreatic cancer progression, and to explore the therapeutic
target of PrP and Notch complex.
Wei Xin is an attending Physician and Associate Residency Program Director of Pathology at University Hospital Case Medical Center, and Assistant Professor at
Case Western Reserve University. He received his medical degree from Shanghai Medical University and Ph.D. from SUNY at Buffalo, and pathology residency
training at University of Michigan. During his career, Dr. Xin has published dozens of paper and gave multiple presentation and workshop at national and international
meetings. He is also in charge of mice histology at Case Comprehensive Cancer Center and the Director of autopsy service of the university hospital.
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